To ingest or rest? Specialized roles of lateral hypothalamic area neurons in coordinating energy balance

Frontiers in Systems Neuroscience

Volumn 9, Issue FEB, 2015, Pages

  Brown, Juliette A ^a,b   Woodworth, Hillary L ^c   Leinninger, Gina M ^b,c  

^a MICHIGAN STATE UNIVERSITY   (United States)

^b Center for Integrative Toxicology   (United States)

^c MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Dopamine; Feeding; Lateral hypothalamic area; Melanin concentrating hormone; Neurotensin; Obesity; Orexin

Indexed keywords

MELANIN CONCENTRATING HORMONE; NEUROPEPTIDE; NEUROTENSIN; OREXIN;

ADDICTION; ANOREXIA; AROUSAL; ARTICLE; ASSOCIATION; BEHAVIOR; CALORIC INTAKE; DRINKING; ENERGY BALANCE; ENERGY EXPENDITURE; HEART RATE; HUMAN; HYDRATION; HYPOTHALAMUS; INGESTION; LOCOMOTION; OBESITY; PARASYMPATHETIC FUNCTION; PHYSICAL ACTIVITY; PHYSIOLOGICAL PROCESS; SENSORIMOTOR FUNCTION; SENSORY STIMULATION; SIGNAL TRANSDUCTION; SYMPATHETIC FUNCTION; THERMOGENESIS;

EID: 84923218489     PISSN: 16625137     EISSN: None     Source Type: Journal    
DOI: 10.3389/fnsys.2015.00009     Document Type: Article

References (441)

1. Abizaid, A., Liu, Z. W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., et al. (2006). Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J. Clin. Invest. 116, 3229–3239. doi: 10.1172/jci29867.
2. Acuna-Goycolea, C., and van den Pol, A. (2004). Glucagon-like peptide 1 excites hypocretin/orexin neurons by direct and indirect mechanisms: implications for viscera-mediated arousal. J. Neurosci. 24, 8141–8152. doi: 10.1523/jneurosci.1607-04.2004.
3. Adamantidis, A. R., Zhang, F., Aravanis, A. M., Deisseroth, K., and De Lecea, L. (2007). Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450, 420–424. doi: 10.1038/nature06310.
4. Adler, E. S., Hollis, J. H., Clarke, I. J., Grattan, D. R., and Oldfield, B. J. (2012). Neurochemical characterization and sexual dimorphism of projections from the brain to abdominal and subcutaneous white adipose tissue in the rat. J. Neurosci. 32, 15913–15921. doi: 10.1523/jneurosci.2591-12.2012.
5. Ahnaou, A., Drinkenburg, W. H., Bouwknecht, J. A., Alcazar, J., Steckler, T., and Dautzenberg, F. M. (2008). Blocking melanin-concentrating hormone MCH1 receptor affects rat sleep-wake architecture. Eur. J. Pharmacol. 579, 177–188. doi: 10.1016/j.ejphar.2007.10.017.
6. Akiyama, M., Yuasa, T., Hayasaka, N., Horikawa, K., Sakurai, T., and Shibata, S. (2004). Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice. Eur J. Neurosci. 20, 3054–3062. doi: 10.1111/j.1460-9568.2004.03749.x.
7. Alam, M. N., Kumar, S., Bashir, T., Suntsova, N., Methippara, M. M., Szymusiak, R., et al. (2005). GABA-mediated control of hypocretin- but not melanin-concentrating hormone-immunoreactive neurones during sleep in rats. J. Physiol. 563, 569–582. doi: 10.1113/jphysiol.2004.076927.
8. Allen, G. V., and Cechetto, D. F. (1995). Neurotensin in the lateral hypothalamic area: origin and function. Neuroscience 69, 533–544. doi: 10.1016/0306-4522(95)00261-g.
9. An, S., Cutler, G., Zhao, J. J., Huang, S. G., Tian, H., Li, W., et al. (2001). Identification and characterization of a melanin-concentrating hormone receptor. Proc. Natl. Acad. Sci. U S A 98, 7576–7581. doi: 10.1074/jbc.m102601200.
10. Anaclet, C., Parmentier, R., Ouk, K., Guidon, G., Buda, C., Sastre, J. P., et al. (2009). Orexin/hypocretin and histamine: distinct roles in the control of wakefulness demonstrated using knock-out mouse models. J. Neurosci. 29, 14423–14438. doi: 10.1523/jneurosci.2604-09.2009.
11. Anand, B. K. (1980). This week’s citation classic: Anand BK and Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale J. Biol. Med. 24, 123–140..
12. Anand, B. K., and Brobeck, J. R. (1951a). Hypothalamic control of food intake in rats and cats. Yale J. Biol. Med. 24, 123–140..
13. Anand, B. K., and Brobeck, J. R. (1951b). Localization of a “feeding center” in the hypothalamus of the rat. Proc. Soc. Exp. Biol. Med. 77, 323–324. doi: 10.3181/00379727-77-18766.
14. Anderson, R. I., Becker, H. C., Adams, B. L., Jesudason, C. D., and Rorick-Kehn, L. M. (2014). Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models. Front. Neurosci. 8:33. doi: 10.3389/fnins.2014.00033.
15. Appelbaum, L., Wang, G., Yokogawa, T., Skariah, G. M., Smith, S. J., Mourrain, P., et al. (2010). Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron 68, 87–98. doi: 10.1016/j.neuron.2010.09.006.
16. Audinat, E., Hermel, J. M., and Crépel, F. (1989). Neurotensin-induced excitation of neurons of the rat’s frontal cortex studied intracellularly in vitro. Exp. Brain Res. 78, 358–368. doi: 10.1007/bf00228907.
17. Aziz, A., Fronczek, R., Maat-Schieman, M., Unmehopa, U., Roelandse, F., Overeem, S., et al. (2008). Hypocretin and melanin-concentrating hormone in patients with Huntington disease. Brain Pathol. 18, 474–483. doi: 10.1111/j.1750-3639.2008.00135.x.
18. Bailey, A. P., Parker, A. G., Colautti, L. A., Hart, L. M., Liu, P., and Hetrick, S. E. (2014). Mapping the evidence for the prevention and treatment of eating disorders in young people. J. Eat. Disord. 2:5. doi: 10.1186/2050-2974-2-5.
19. Baird, J. P., Gray, N. E., and Fischer, S. G. (2006a). Effects of neuropeptide Y on feeding microstructure: dissociation of appetitive and consummatory actions. Behav. Neurosci. 120, 937–951. doi: 10.1037/0735-7044.120.4.937.
20. Baird, J. P., Rios, C., Gray, N. E., Walsh, C. E., Fischer, S. G., and Pecora, A. L. (2006b). Effects of melanin-concentrating hormone on licking microstructure and brief-access taste responses. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R1265–R1274. doi: 10.1152/ajpregu.00143.2006.
21. Baird, J. P., Rios, C., Loveland, J. L., Beck, J., Tran, A., and Mahoney, C. E. (2008). Effects of hindbrain melanin-concentrating hormone and neuropeptide Y administration on licking for water, saccharin and sucrose solutions. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R329–R343. doi: 10.1152/ajpregu.00611.2006.
22. Baker, J. D., Hawkins, M. F., Baumeister, A. A., and Nagy, M. (1989). Microinjection of neurotensin into the CNS induces hyperdipsia in the rat. Pharmacol. Biochem. Behav. 33, 7–10. doi: 10.1016/0091-3057(89)90420-6.
23. Basso, A. M., Bratcher, N. A., Gallagher, K. B., Cowart, M. D., Zhao, C., Sun, M., et al. (2006). Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety. Eur. J. Pharmacol. 540, 115–120. doi: 10.1016/j.ejphar.2006.04.043.
24. Baumann, C. R., Bassetti, C. L., Valko, P. O., Haybaeck, J., Keller, M., Clark, E., et al. (2009). Loss of hypocretin (orexin) neurons with traumatic brain injury. Ann. Neurol. 66, 555–559. doi: 10.1002/ana.21836.
25. Baumann, C. R., Stocker, R., Imhof, H. G., Trentz, O., Hersberger, M., Mignot, E., et al. (2005). Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury. Neurology 65, 147–149. doi: 10.1212/01.wnl.0000167605.02541.f2.
26. Bayer, L., Eggermann, E., Serafin, M., Saint-Mleux, B., Machard, D., Jones, B., et al. (2001). Orexins (hypocretins) directly excite tuberomammillary neurons. Eur J. Neurosci. 14, 1571–1575. doi: 10.1046/j.0953-816x.2001.01777.x.
27. Bean, A. J., During, M. J., Deutch, A. Y., and Roth, R. H. (1989). Effects of dopamine depletion on striatal neurotensin: biochemical and immunohistochemical studies. J. Neurosci. 9, 4430–4438..
28. Beck, B., Burlet, A., Nicolas, J. P., and Burlet, C. (1989). Neurotensin in microdissected brain nuclei and in the pituitary of the lean and obese Zucker rats. Neuropeptides 13, 1–7. doi: 10.1016/0143-4179(89)90014-0.
29. Beck, B., Burlet, A., Nicolas, J. P., and Burlet, C. (1990). Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats. J. Nutr. 120, 806–811..
30. Beck, B., Stricker-Krongrad, A., Burlet, A., Nicolas, J. P., and Burlet, C. (1992). Changes in hypothalamic neurotensin concentrations and food intake in rats fed a high fat diet. Int. J. Obes. Relat. Metab. Disord. 16, 361–366..
31. Beck, B., Stricker-Krongrad, A., Richy, S., and Burlet, C. (1998). Evidence that hypothalamic neurotensin signals leptin effects on feeding behavior in normal and fat-preferring rats. Biochem. Biophys. Res. Commun. 252, 634–638. doi: 10.1006/bbrc.1998.9712.
32. Becskei, C., Riediger, T., Hernádfalvy, N., Arsenijevic, D., Lutz, T. A., and Langhans, W. (2008). Inhibitory effects of lipopolysaccharide on hypothalamic nuclei implicated in the control of food intake. Brain Behav. Immun. 22, 56–64. doi: 10.1016/j.bbi.2007.06.002.
33. Behbehani, M. M., Park, M. R., and Clement, M. E. (1988). Interactions between the lateral hypothalamus and the periaqueductal gray. J. Neurosci. 8, 2780–2787..
34. Behbehani, M. M., and Pert, A. (1984). A mechanism for the analgesic effect of neurotensin as revealed by behavioral and electrophysiological techniques. Brain Res. 324, 35–42. doi: 10.1016/0006-8993(84)90619-x.
35. Behbehani, M. M., Shipley, M. T., and Mclean, J. H. (1987). Effect of neurotensin on neurons in the periaqueductal gray: an in vitro study. J. Neurosci. 7, 2035–2040..
36. Berridge, K. C., Ho, C. Y., Richard, J. M., and Difeliceantonio, A. G. (2010). The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res. 1350, 43–64. doi: 10.1016/j.brainres.2010.04.003.
37. Berthoud, H. R. (2012). The neurobiology of food intake in an obesogenic environment. Proc. Nutr. Soc. 71, 478–487. doi: 10.1017/s0029665112000602.
38. Beuckmann, C. T., Sinton, C. M., Williams, S. C., Richardson, J. A., Hammer, R. E., Sakurai, T., et al. (2004). Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J. Neurosci. 24, 4469–4477. doi: 10.1523/jneurosci.5560-03.2004.
39. Binder, E. B., Kinkead, B., Owens, M. J., Kilts, C. D., and Nemeroff, C. B. (2001). Enhanced neurotensin neurotransmission is involved in the clinically relevant behavioral effects of antipsychotic drugs: evidence from animal models of sensorimotor gating. J. Neurosci. 21, 601–608..
40. Bissette, G., Luttinger, D., Mason, G. A., Hernandez, D. E., and Loosen, P. T. (1982). Neurotensin and thermoregulation. Ann. N Y Acad. Sci. 400, 268–282. doi: 10.1111/j.1749-6632.1982.tb31575.x.
41. Bissette, G., Nemeroff, C. B., Loosen, P. T., Prange, A. J. Jr., and Lipton, M. A. (1976). Hypothermia and intolerance to cold induced by intracisternal administration of the hypothalamic peptide neurotensin. Nature 262, 607–609. doi: 10.1038/262607a0.
42. Bittencourt, J. C., and Elias, C. F. (1998). Melanin-concentrating hormone and neuropeptide EI projections from the lateral hypothalamic area and zona incerta to the medial septal nucleus and spinal cord: a study using multiple neuronal tracers. Brain Res. 805, 1–19. doi: 10.1016/s0006-8993(98)00598-8.
43. Bittencourt, J. C., Presse, F., Arias, C., Peto, C., Vaughan, J., Nahon, J. L., et al. (1992). The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J. Comp. Neurol. 319, 218–245. doi: 10.1002/cne.903190204.
44. Blaha, C. D., Coury, A., Fibiger, H. C., and Phillips, A. G. (1990). Effects of neurotensin on dopamine release and metabolism in the rat striatum and nucleus accumbens: cross-validation using in vivo voltammetry and microdialysis. Neuroscience 34, 699–705. doi: 10.1016/0306-4522(90)90176-5.
45. Blouin, A. M., Fried, I., Wilson, C. L., Staba, R. J., Behnke, E. J., Lam, H. A., et al. (2013). Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction. Nat. Commun. 4:1547. doi: 10.1038/ncomms2461.
46. Borgland, S. L., Chang, S. J., Bowers, M. S., Thompson, J. L., Vittoz, N., Floresco, S. B., et al. (2009). Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. J. Neurosci. 29, 11215–11225. doi: 10.1523/jneurosci.6096-08.2009.
47. Borgland, S. L., Taha, S. A., Sarti, F., Fields, H. L., and Bonci, A. (2006). Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49, 589–601. doi: 10.1016/j.neuron.2006.01.016.
48. Borowsky, B., Durkin, M. M., Ogozalek, K., Marzabadi, M. R., Deleon, J., Lagu, B., et al. (2002). Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat. Med. 8, 825–830. doi: 10.1038/nm0902-1039b.
49. Boules, M., Cusack, B., Zhao, L., Fauq, A., Mccormick, D. J., and Richelson, E. (2000). A novel neurotensin peptide analog given extracranially decreases food intake and weight in rodents. Brain Res. 865, 35–44. doi: 10.1016/s0006-8993(00)02187-9.
50. Bourgin, P., Huitrón-Résendiz, S., Spier, A. D., Fabre, V., Morte, B., Criado, J. R., et al. (2000). Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J. Neurosci. 20, 7760–7765..
51. Bray, G. A., and Ryan, D. H. (2014). Update on obesity pharmacotherapy. Ann. N Y Acad. Sci. 1311, 1–13. doi: 10.1111/nyas.12328.
52. Brisbare-Roch, C., Dingemanse, J., Koberstein, R., Hoever, P., Aissaoui, H., Flores, S., et al. (2007). Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat. Med. 13, 150–155. doi: 10.1038/nm0507-525.
53. Brischoux, F., Cvetkovic, V., Griffond, B., Fellmann, D., and Risold, P. Y. (2002). Time of genesis determines projection and neurokinin-3 expression patterns of diencephalic neurons containing melanin-concentrating hormone. Eur J. Neurosci. 16, 1672–1680. doi: 10.1046/j.1460-9568.2002.02229.x.
54. Brouard, A., Heaulme, M., Leyris, R., Pelaprat, D., Gully, D., Kitabgi, P., et al. (1994). SR 48692 inhibits neurotensin-induced [3H]dopamine release in rat striatal slices and mesencephalic cultures. Eur. J. Pharmacol. 253, 289–291. doi: 10.1016/0014-2999(94)90204-6.
55. Bruning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., et al. (2000). Role of brain insulin receptor in control of body weight and reproduction. Science 289, 2122–2125. doi: 10.1126/science.289.5487.2122.
56. Burdakov, D., Gerasimenko, O., and Verkhratsky, A. (2005). Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J. Neurosci. 25, 2429–2433. doi: 10.1523/jneurosci.4925-04.2005.
57. Cai, X. J., Lister, C. A., Buckingham, R. E., Pickavance, L., Wilding, J., Arch, J. R., et al. (2000). Down-regulation of orexin gene expression by severe obesity in the rats: studies in Zucker fatty and zucker diabetic fatty rats and effects of rosiglitazone. Brain Res. Mol. Brain Res. 77, 131–137. doi: 10.1016/s0169-328x(00)00041-3.
58. Cai, X. J., Widdowson, P. S., Harrold, J., Wilson, S., Buckingham, R. E., Arch, J. R., et al. (1999). Hypothalamic orexin expression: modulation by blood glucose and feeding. Diabetes 48, 2132–2137. doi: 10.2337/diabetes.48.11.2132.
59. Carraway, R., and Leeman, S. E. (1973). The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J. Biol. Chem. 248, 6854–6861..
60. Carter, M. E., Adamantidis, A., Ohtsu, H., Deisseroth, K., and De Lecea, L. (2009). Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J. Neurosci. 29, 10939–10949. doi: 10.1523/JNEUROSCI.1205-09.2009.
61. Carter, M. E., Brill, J., Bonnavion, P., Huguenard, J. R., Huerta, R., and De Lecea, L. (2012). Mechanism for Hypocretin-mediated sleep-to-wake transitions. Proc. Natl. Acad. Sci. U S A 109, E2635–E2644. doi: 10.1073/pnas.1202526109.
62. Carter, M. E., Soden, M. E., Zweifel, L. S., and Palmiter, R. D. (2013). Genetic identification of a neural circuit that suppresses appetite. Nature 503, 111–114. doi: 10.1038/nature12596.
63. Cason, A. M., and Aston-Jones, G. (2013a). Attenuation of saccharin-seeking in rats by orexin/hypocretin receptor 1 antagonist. Psychopharmacology (Berl) 228, 499–507. doi: 10.1007/s00213-013-3051-7.
64. Cason, A. M., and Aston-Jones, G. (2013b). Role of orexin/hypocretin in conditioned sucrose-seeking in rats. Psychopharmacology (Berl) 226, 155–165. doi: 10.1007/s00213-012-2902-y.
65. Castel, M. N., Stutzmann, J. M., Lucas, M., Lafforgue, J., and Blanchard, J. C. (1989). Effects of ICV administration of neurotensin and analogs on EEG in rats. Peptides 10, 95–101. doi: 10.1016/0196-9781(89)90083-1.
66. Cervo, L., Rossi, C., Tatarczynska, E., and Samanin, R. (1992). Antidepressant-like effect of neurotensin administered in the ventral tegmental area in the forced swimming test. Psychopharmacology (Berl) 109, 369–372. doi: 10.1007/bf02245885.
67. Chakfe, Y., and Bourque, C. W. (2000). Excitatory peptides and osmotic pressure modulate mechanosensitive cation channels in concert. Nat. Neurosci. 3, 572–579. doi: 10.1038/78732.
68. Chambers, J., Ames, R. S., Bergsma, D., Muir, A., Fitzgerald, L. R., Hervieu, G., et al. (1999). Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature 400, 261–265. doi: 10.1016/s0014-5793(99)01092-3.
69. Checler, F., Vincent, J. P., and Kitabgi, P. (1983). Degradation of neurotensin by rat brain synaptic membranes: involvement of a thermolysin-like metalloendopeptidase (enkephalinase), angiotensin-converting enzyme and other unidentified peptidases. J. Neurochem. 41, 375–384. doi: 10.1111/j.1471-4159.1983.tb04753.x.
70. Chee, M. J., Pissios, P., and Maratos-Flier, E. (2013). Neurochemical characterization of neurons expressing melanin-concentrating hormone receptor 1 in the mouse hypothalamus. J. Comp. Neurol. 521, 2208–2234. doi: 10.1002/cne.23273.
71. Chee, M. J., Pissios, P., Prasad, D., and Maratos-Flier, E. (2014). Expression of melanin-concentrating hormone receptor 2 protects against diet-induced obesity in male mice. Endocrinology 155, 81–88. doi: 10.1210/en.2013-1738.
72. Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., et al. (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98, 437–451. doi: 10.1016/s0092-8674(00)81973-x.
73. Chen, Y., Hu, C., Hsu, C. K., Zhang, Q., Bi, C., Asnicar, M., et al. (2002). Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology 143, 2469–2477. doi: 10.1210/en.143.7.2469.
74. Chen, X. W., Mu, Y., Huang, H. P., Guo, N., Zhang, B., Fan, S. Y., et al. (2008). Hypocretin-1 potentiates NMDA receptor-mediated somatodendritic secretion from locus ceruleus neurons. J. Neurosci. 28, 3202–3208. doi: 10.1523/jneurosci.4426-07.2008.
75. Chen, M., Woods, S. C., and Porte, D. Jr. (1975). Effect of cerebral intraventricular insulin on pancreatic insulin secretion in the dog. Diabetes 24, 910–914. doi: 10.2337/diabetes.24.10.910.
76. Choi, D. L., Davis, J. F., Fitzgerald, M. E., and Benoit, S. C. (2010). The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats. Neuroscience 167, 11–20. doi: 10.1016/j.neuroscience.2010.02.002.
77. Chou, T. C., Lee, C. E., Lu, J., Elmquist, J. K., Hara, J., Willie, J. T., et al. (2001). Orexin (hypocretin) neurons contain dynorphin. J. Neurosci. 21:RC168..
78. Chua, S. C. Jr., Chung, W. K., Wu-Peng, X. S., Zhang, Y., Liu, S. M., Tartaglia, L., et al. (1996). Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271, 994–996. doi: 10.1126/science.271.5251.994.
79. Chung, S., Hopf, F. W., Nagasaki, H., Li, C. Y., Belluzzi, J. D., Bonci, A., et al. (2009). The melanin-concentrating hormone system modulates cocaine reward. Proc. Natl. Acad. Sci. U S A 106, 6772–6777. doi: 10.1073/pnas.0811331106.
80. Clegg, D. J., Air, E. L., Benoit, S. C., Sakai, R. S., Seeley, R. J., and Woods, S. C. (2003). Intraventricular melanin-concentrating hormone stimulates water intake independent of food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R494–R499. doi: 10.1152/ajpregu.00399.2002.
81. Clegg, D. J., Air, E. L., Woods, S. C., and Seeley, R. J. (2002). Eating elicited by orexin-a, but not melanin-concentrating hormone, is opioid mediated. Endocrinology 143, 2995–3000. doi: 10.1210/en.143.8.2995.
82. Clement, O., Sapin, E., Libourel, P. A., Arthaud, S., Brischoux, F., Fort, P., et al. (2012). The lateral hypothalamic area controls paradoxical (REM) sleep by means of descending projections to brainstem GABAergic neurons. J. Neurosci. 32, 16763–16774. doi: 10.1523/jneurosci.1885-12.2012.
83. Clineschmidt, B. V., Mcguffin, J. C., and Bunting, P. B. (1979). Neurotensin: antinocisponsive action in rodents. Eur. J. Pharmacol. 54, 129–139. doi: 10.1016/0014-2999(79)90415-1.
84. Cohen, P., Zhao, C., Cai, X., Montez, J. M., Rohani, S. C., Feinstein, P., et al. (2001). Selective deletion of leptin receptor in neurons leads to obesity. J. Clin. Invest. 108, 1113–1121. doi: 10.1172/jci200113914.
85. Cone, J. J., Mccutcheon, J. E., and Roitman, M. F. (2014). Ghrelin acts as an interface between physiological state and phasic dopamine signaling. J. Neurosci. 34, 4905–4913. doi: 10.1523/jneurosci.4404-13.2014.
86. Cristino, L., Busetto, G., Imperatore, R., Ferrandino, I., Palomba, L., Silvestri, C., et al. (2013). Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. Proc. Natl. Acad. Sci. U S A 110, E2229–E2238. doi: 10.1073/pnas.1219485110.
87. Crocker, A., España, R. A., Papadopoulou, M., Saper, C. B., Faraco, J., Sakurai, T., et al. (2005). Concomitant loss of dynorphin, NARP and orexin in narcolepsy. Neurology 65, 1184–1188. doi: 10.1212/01.wnl.0000168173.71940.ab.
88. Cui, H., Cai, F., and Belsham, D. D. (2006). Leptin signaling in neurotensin neurons involves STAT, MAP kinases ERK1/2 and p38 through c-Fos and ATF1. Faseb J. 20, 2654–2656. doi: 10.1096/fj.06-5989fje.
89. Cui, H., Sohn, J. W., Gautron, L., Funahashi, H., Williams, K. W., Elmquist, J. K., et al. (2012). Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area. J. Comp. Neurol. 520, 4168–4183. doi: 10.1002/cne.23145.
90. Cvetkovic, V., Brischoux, F., Jacquemard, C., Fellmann, D., Griffond, B., and Risold, P. Y. (2004). Characterization of subpopulations of neurons producing melanin-concentrating hormone in the rat ventral diencephalon. J. Neurochem. 91, 911–919. doi: 10.1111/j.1471-4159.2004.02776.x.
91. Dalal, M. A., Schuld, A., Haack, M., Uhr, M., Geisler, P., Eisensehr, I., et al. (2001). Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients. Neurology 56, 1749–1751. doi: 10.1212/wnl.56.12.1749.
92. Date, Y., Ueta, Y., Yamashita, H., Yamaguchi, H., Matsukura, S., Kangawa, K., et al. (1999). Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc. Natl. Acad. Sci. U S A 96, 748–753. doi: 10.1073/pnas.96.2.748.
93. Dayyeh, B. K., Lautz, D. B., and Thompson, C. C. (2010). Gastrojejunal stoma diameter predicts weight regain after Roux-en-Y gastric bypass. Clin. Gastroenterol. Hepatol. 9, 228–233. doi: 10.1016/j.cgh.2010.11.004.
94. de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X., Foye, P. E., Danielson, P. E., et al. (1998). The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. U S A 95, 322–327. doi: 10.1073/pnas.95.1.322.
95. Delgado, J. M., and Anand, B. K. (1953). Increase of food intake induced by electrical stimulation of the lateral hypothalamus. Am. J. Physiol. 172, 162–168..
96. Deutch, A. Y., Bean, A. J., Bissette, G., Nemeroff, C. B., Robbins, R. J., and Roth, R. H. (1987). Stress-induced alterations in neurotensin, somatostatin and corticotropin-releasing factor in mesotelencephalic dopamine system regions. Brain Res. 417, 350–354. doi: 10.1016/0006-8993(87)90462-8.
97. Diano, S., Horvath, B., Urbanski, H. F., Sotonyi, P., and Horvath, T. L. (2003). Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets. Endocrinology 144, 3774–3778. doi: 10.1210/en.2003-0274.
98. Diniz Behn, C. G., Klerman, E. B., Mochizuki, T., Lin, S. C., and Scammell, T. E. (2010). Abnormal sleep/wake dynamics in orexin knockout mice. Sleep 33, 297–306..
99. Domingos, A. I., Sordillo, A., Dietrich, M. O., Liu, Z. W., Tellez, L. A., Vaynshteyn, J., et al. (2013). Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar. Elife 2:e01462. doi: 10.7554/elife.01462.
100. Dubuc, I., Sarret, P., Labbé-Jullié, C., Botto, J. M., Honoré, E., Bourdel, E., et al. (1999). Identification of the receptor subtype involved in the analgesic effect of neurotensin. J. Neurosci. 19, 503–510..
101. Duncan, E. A., Proulx, K., and Woods, S. C. (2005). Central administration of melanin-concentrating hormone increases alcohol and sucrose/quinine intake in rats. Alcohol. Clin. Exp. Res. 29, 958–964. doi: 10.1097/01.alc.0000167741.42353.10.
102. Dundas, B., Harris, M., and Narasimhan, M. (2007). Psychogenic polydipsia review: etiology, differential and treatment. Curr. Psychiatry Rep. 9, 236–241. doi: 10.1007/s11920-007-0025-7.
103. Dunnett, S. B., Lane, D. M., and Winn, P. (1985). Ibotenic acid lesions of the lateral hypothalamus: comparison with 6-hydroxydopamine-induced sensorimotor deficits. Neuroscience 14, 509–518. doi: 10.1016/0306-4522(85)90306-9.
104. Edwards, C. M., Abusnana, S., Sunter, D., Murphy, K. G., Ghatei, M. A., and Bloom, S. R. (1999). The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin. J. Endocrinol. 160, R7–R12. doi: 10.1677/joe.0.160r007.
105. Eggermann, E., Bayer, L., Serafin, M., Saint-Mleux, B., Bernheim, L., Machard, D., et al. (2003). The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarization. J. Neurosci. 23, 1557–1562..
106. Elias, C. F., Lee, C. E., Kelly, J. F., Ahima, R. S., Kuhar, M., Saper, C. B., et al. (2001). Characterization of CART neurons in the rat and human hypothalamus. J. Comp. Neurol. 432, 1–19. doi: 10.1002/cne.1085.
107. Elias, C. F., Saper, C. B., Maratos-Flier, E., Tritos, N. A., Lee, C., Kelly, J., et al. (1998). Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J. Comp. Neurol. 402, 442–459. doi: 10.1002/(sici)1096-9861(19981228)402:4<442::aid-cne2>3.3.co;2-i.
108. Elliott, P. J., Chan, J., Parker, Y. M., and Nemeroff, C. B. (1986). Behavioral effects of neurotensin in the open field: structure-activity studies. Brain Res. 381, 259–265. doi: 10.1016/0006-8993(86)90075-2.
109. Elliott, P. J., and Nemeroff, C. B. (1986). Repeated neurotensin administration in the ventral tegmental area: effects on baseline and D-amphetamine-induced locomotor activity. Neurosci. Lett. 68, 239–244. doi: 10.1016/0304-3940(86)90149-7.
110. Eriksson, K. S., Sergeeva, O., Brown, R. E., and Haas, H. L. (2001). Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J. Neurosci. 21, 9273–9279..
111. Ervin, G. N., Birkemo, L. S., Nemeroff, C. B., and Prange, A. J. Jr. (1981). Neurotensin blocks certain amphetamine-induced behaviours. Nature 291, 73–76. doi: 10.1038/291073a0.
112. España, R. A., Melchior, J. R., Roberts, D. C., and Jones, S. R. (2011). Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration. Psychopharmacology (Berl) 214, 415–426. doi: 10.1007/s00213-010-2048-8.
113. España, R. A., Oleson, E. B., Locke, J. L., Brookshire, B. R., Roberts, D. C., and Jones, S. R. (2010). The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system. Eur J. Neurosci. 31, 336–348. doi: 10.1111/j.1460-9568.2009.07065.x.
114. España, R. A., Plahn, S., and Berridge, C. W. (2002). Circadian-dependent and circadian-independent behavioral actions of hypocretin/orexin. Brain Res. 943, 224–236. doi: 10.1016/s0006-8993(02)02653-7.
115. Estabrooke, I. V., Mccarthy, M. T., Ko, E., Chou, T. C., Chemelli, R. M., Yanagisawa, M., et al. (2001). Fos expression in orexin neurons varies with behavioral state. J. Neurosci. 21, 1656–1662..
116. Fadel, J., and Deutch, A. Y. (2002). Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience 111, 379–387. doi: 10.1016/s0306-4522(02)00017-9.
117. Fang, F. G., Moreau, J. L., and Fields, H. L. (1987). Dose-dependent antinociceptive action of neurotensin microinjected into the rostroventromedial medulla of the rat. Brain Res. 420, 171–174. doi: 10.1016/0006-8993(87)90255-1.
118. Farkas, R. H., Chien, P. Y., Nakajima, S., and Nakajima, Y. (1997). Neurotensin and dopamine D2 activation oppositely regulate the same K+ conductance in rat midbrain dopaminergic neurons. Neurosci. Lett. 231, 21–24. doi: 10.1016/s0304-3940(97)00530-2.
119. Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., et al. (1999). Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med. 341, 879–884. doi: 10.1056/nejm199909163411204.
120. Feifel, D., Goldenberg, J., Melendez, G., and Shilling, P. D. (2010). The acute and subchronic effects of a brain-penetrating, neurotensin-1 receptor agonist on feeding, body weight and temperature. Neuropharmacology 58, 195–198. doi: 10.1016/j.neuropharm.2009.07.001.
121. Fekete, C., Wittmann, G., Liposits, Z., and Lechan, R. M. (2004). Origin of cocaine- and amphetamine-regulated transcript (CART)-immunoreactive innervation of the hypothalamic paraventricular nucleus. J. Comp. Neurol. 469, 340–350. doi: 10.1002/cne.10999.
122. Feurle, G. E. (1998). Xenin–a review. Peptides 19, 609–615. doi: 10.1016/s0196-9781(97)00378-1.
123. Flegal, K. M., Carroll, M. D., Kit, B. K., and Ogden, C. L. (2012). Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA 307, 491–497. doi: 10.1001/jama.2012.39.
124. Foo, K. S., Brismar, H., and Broberger, C. (2008). Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. Neuroscience 156, 563–579. doi: 10.1016/j.neuroscience.2008.07.054.
125. Fukunaka, Y., Shinkai, T., Hwang, R., Hori, H., Utsunomiya, K., Sakata, S., et al. (2007). The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia. Neuromolecular Med. 9, 292–297. doi: 10.1007/s12017-007-8001-2.
126. Funato, H., Tsai, A. L., Willie, J. T., Kisanuki, Y., Williams, S. C., Sakurai, T., et al. (2009). Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 9, 64–76. doi: 10.1016/j.cmet.2008.10.010.
127. Furutani, N., Hondo, M., Kageyama, H., Tsujino, N., Mieda, M., Yanagisawa, M., et al. (2013). Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness States. PLoS One 8:e62391. doi: 10.1371/journal.pone.0062391.
128. Gaykema, R. P., and Goehler, L. E. (2009). Lipopolysaccharide challenge-induced suppression of Fos in hypothalamic orexin neurons: their potential role in sickness behavior. Brain Behav. Immun. 23, 926–930. doi: 10.1016/j.bbi.2009.03.005.
129. Georgescu, D., Sears, R. M., Hommel, J. D., Barrot, M., Bolaños, C. A., Marsh, D. J., et al. (2005). The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. J. Neurosci. 25, 2933–2940. doi: 10.1523/jneurosci.1714-04.2005.
130. Gerashchenko, D., Kohls, M. D., Greco, M., Waleh, N. S., Salin-Pascual, R., Kilduff, T. S., et al. (2001). Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J. Neurosci. 21, 7273–7283..
131. Glick, M., Segal-Lieberman, G., Cohen, R., and Kronfeld-Schor, N. (2009). Chronic MCH infusion causes a decrease in energy expenditure and body temperature and an increase in serum IGF-1 levels in mice. Endocrine 36, 479–485. doi: 10.1007/s12020-009-9252-5.
132. Glimcher, P. W., Giovino, A. A., and Hoebel, B. G. (1987). Neurotensin self-injection in the ventral tegmental area. Brain Res. 403, 147–150. doi: 10.1016/0006-8993(87)90134-x.
133. Glimcher, P. W., Margolin, D. H., Giovino, A. A., and Hoebel, B. G. (1984). Neurotensin: a new’reward peptide’. Brain Res. 291, 119–124. doi: 10.1016/0006-8993(84)90657-7.
134. Goforth, P. B., Leinninger, G. M., Patterson, C. M., Satin, L. S., and Myers, M. G. Jr. (2014). Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms. J. Neurosci. 34, 11405–11415. doi: 10.1523/jneurosci.5167-13.2014.
135. Goto, M., Canteras, N. S., Burns, G., and Swanson, L. W. (2005). Projections from the subfornical region of the lateral hypothalamic area. J. Comp. Neurol. 493, 412–438. doi: 10.1002/cne.20764.
136. Grabauskas, G., and Moises, H. C. (2003). Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin. J. Physiol. 549, 37–56. doi: 10.1113/jphysiol.2002.029546.
137. Griffiths, E. C., Slater, P., and Widdowson, P. S. (1986). The hypothermic action of carbachol in the rat brain periaqueductal grey area may involve neurotensin. Br. J. Pharmacol. 88, 653–658. doi: 10.1111/j.1476-5381.1986.tb10247.x.
138. Grossberg, A. J., Zhu, X., Leinninger, G. M., Levasseur, P. R., Braun, T. P., Myers, M. G., et al. (2011). Inflammation-induced lethargy is mediated by suppression of orexin neuron activity. J. Neurosci. 31, 11376–11386. doi: 10.1523/jneurosci.2311-11.2011.
139. Grossman, S. P., Dacey, D., Halaris, A. E., Collier, T., and Routtenberg, A. (1978). Aphagia and adipsia after preferential destruction of nerve cell bodies in hypothalamus. Science 202, 537–539. doi: 10.1126/science.705344.
140. Gully, D., Canton, M., Boigegrain, R., Jeanjean, F., Molimard, J. C., Poncelet, M., et al. (1993). Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc. Natl. Acad. Sci. U S A 90, 65–69. doi: 10.1073/pnas.90.1.65.
141. Hagan, J. J., Leslie, R. A., Patel, S., Evans, M. L., Wattam, T. A., Holmes, S., et al. (1999). Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc. Natl. Acad. Sci. U S A 96, 10911–10916. doi: 10.1073/pnas.96.19.10911.
142. Hahn, J. D., and Swanson, L. W. (2010). Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat. Brain Res. Rev. 64, 14–103. doi: 10.1016/j.brainresrev.2010.02.002.
143. Håkansson, M., de Lecea, L., Sutcliffe, J. G., Yanagisawa, M., and Meister, B. (1999). Leptin receptor- and STAT3-immunoreactivities in hypocretin/orexin neurones of the lateral hypothalamus. J. Neuroendocrinol. 11, 653–663. doi: 10.1046/j.1365-2826.1999.00378.x.
144. Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., et al. (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–546. doi: 10.1126/science.7624777.
145. Hara, J., Beuckmann, C. T., Nambu, T., Willie, J. T., Chemelli, R. M., Sinton, C. M., et al. (2001). Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia and obesity. Neuron 30, 345–354. doi: 10.1016/s0896-6273(01)00293-8.
146. Harris, G. C., and Aston-Jones, G. (2006). Arousal and reward: a dichotomy in orexin function. Trends Neurosci. 29, 571–577. doi: 10.1016/j.tins.2006.08.002.
147. Harris, G. C., Wimmer, M., and Aston-Jones, G. (2005). A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437, 556–559. doi: 10.1038/nature04071.
148. Hart, S., Franklin, R. C., Russell, J., and Abraham, S. (2013). A review of feeding methods used in the treatment of anorexia nervosa. J. Eat. Disord. 1:36. doi: 10.1186/2050-2974-1-36.
149. Harthoorn, L. F., Sañé, A., Nethe, M., and Van Heerikhuize, J. J. (2005). Multi-transcriptional profiling of melanin-concentrating hormone and orexin-containing neurons. Cell. Mol. Neurobiol. 25, 1209–1223. doi: 10.1007/s10571-005-8184-8.
150. Hasegawa, E., Yanagisawa, M., Sakurai, T., and Mieda, M. (2014). Orexin neurons suppress narcolepsy via 2 distinct efferent pathways. J. Clin. Invest. 124, 604–616. doi: 10.1172/jci71017.
151. Hassani, O. K., Henny, P., Lee, M. G., and Jones, B. E. (2010). GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep. Eur J. Neurosci. 32, 448–457. doi: 10.1111/j.1460-9568.2010.07295.x.
152. Hassani, O. K., Lee, M. G., and Jones, B. E. (2009). Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc. Natl. Acad. Sci. U S A 106, 2418–2422. doi: 10.1073/pnas.0811400106.
153. Hawes, B. E., Kil, E., Green, B., O’neill, K., Fried, S., and Graziano, M. P. (2000). The melanin-concentrating hormone receptor couples to multiple G proteins to activate diverse intracellular signaling pathways. Endocrinology 141, 4524–4532. doi: 10.1210/en.141.12.4524.
154. Hawken, E. R., Crookall, J. M., Reddick, D., Millson, R. C., Milev, R., and Delva, N. (2009). Mortality over a 20-year period in patients with primary polydipsia associated with schizophrenia: a retrospective study. Schizophr. Res. 107, 128–133. doi: 10.1016/j.schres.2008.09.029.
155. Hawkins, M. F. (1986a). Aphagia in the rat following microinjection of neurotensin into the ventral tegmental area. Life Sci. 38, 2383–2388. doi: 10.1016/0024-3205(86)90606-5.
156. Hawkins, M. F. (1986b). Central nervous system neurotensin and feeding. Physiol. Behav. 36, 1–8. doi: 10.1016/0031-9384(86)90064-8.
157. Hawkins, M. F., Barkemeyer, C. A., and Tulley, R. T. (1986). Synergistic effects of dopamine agonists and centrally administered neurotensin on feeding. Pharmacol. Biochem. Behav. 24, 1195–1201. doi: 10.1016/0091-3057(86)90170-x.
158. Haynes, A. C., Jackson, B., Chapman, H., Tadayyon, M., Johns, A., Porter, R. A., et al. (2000). A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul. Pept. 96, 45–51. doi: 10.1016/s0167-0115(00)00199-3.
159. Haynes, A. C., Jackson, B., Overend, P., Buckingham, R. E., Wilson, S., Tadayyon, M., et al. (1999). Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat. Peptides 20, 1099–1105. doi: 10.1016/s0196-9781(99)00105-9.
160. Hermans, E., Maloteaux, J. M., and Octave, J. N. (1992). Phospholipase C activation by neurotensin and neuromedin N in Chinese hamster ovary cells expressing the rat neurotensin receptor. Brain Res. Mol. Brain Res. 15, 332–338. doi: 10.1016/0169-328x(92)90126-v.
161. Hernandez, L., and Hoebel, B. G. (1988). Feeding and hypothalamic stimulation increase dopamine turnover in the accumbens. Physiol. Behav. 44, 599–606. doi: 10.1016/0031-9384(88)90324-1.
162. Herve, D., Tassin, J. P., Studler, J. M., Dana, C., Kitabgi, P., Vincent, J. P., et al. (1986). Dopaminergic control of 125I-labeled neurotensin binding site density in corticolimbic structures of the rat brain. Proc. Natl. Acad. Sci. U S A 83, 6203–6207. doi: 10.1073/pnas.83.16.6203.
163. Hetherington, A. W., and Ranson, S. W. (1939). Experimental hyothamico-hypophyseal obesity in the rat. Exp. Biol. Med. 41, 465–466. doi: 10.3181/00379727-41-10711p.
164. Hetherington, A. W., and Ranson, S. W. (1940). Hypothalamic lesions and adiposity in the rat. Anatomical Record 78, 149–172. doi: 10.1002/ar.1090780203.
165. Heydendael, W., Sharma, K., Iyer, V., Luz, S., Piel, D., Beck, S., et al. (2011). Orexins/hypocretins act in the posterior paraventricular thalamic nucleus during repeated stress to regulate facilitation to novel stress. Endocrinology 152, 4738–4752. doi: 10.1210/en.2011-1652.
166. Higgins, G. A., Hoffman, G. E., Wray, S., and Schwaber, J. S. (1984). Distribution of neurotensin-immunoreactivity within baroreceptive portions of the nucleus of the tractus solitarius and the dorsal vagal nucleus of the rat. J. Comp. Neurol. 226, 155–164. doi: 10.1002/cne.902260202.
167. Hoang, Q. V., Bajic, D., Yanagisawa, M., Nakajima, S., and Nakajima, Y. (2003). Effects of orexin (hypocretin) on GIRK channels. J. Neurophysiol. 90, 693–702. doi: 10.1152/jn.00001.2003.
168. Hoebel, B. G. (1965). Hypothalamic lesions by electrocauterization: disinhibition of feeding and self-stimulation. Science 149, 452–453. doi: 10.1126/science.149.3682.452.
169. Hoebel, B. G., and Teitelbaum, P. (1962). Hypothalamic control of feeding and self-stimulation. Science 135, 375–377. doi: 10.1126/science.135.3501.375.
170. Holmqvist, T., Johansson, L., Ostman, M., Ammoun, S., Akerman, K. E., and Kukkonen, J. P. (2005). OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms. J. Biol. Chem. 280, 6570–6579. doi: 10.1074/jbc.m407397200.
171. Honda, Y., Doi, Y., Ninomiya, R., and Ninomiya, C. (1986). Increased frequency of non-insulin-dependent diabetes mellitus among narcoleptic patients. Sleep 9, 254–259..
172. Honda, M., Eriksson, K. S., Zhang, S., Tanaka, S., Lin, L., Salehi, A., et al. (2009). IGFBP3 colocalizes with and regulates hypocretin (orexin). PLoS One 4:e4254. doi: 10.1371/journal.pone.0004254.
173. Horvath, T. L., Diano, S., and van den Pol, A. N. (1999a). Synaptic interaction between hypocretin (orexin) and neuropeptide Y cells in the rodent and primate hypothalamus: a novel circuit implicated in metabolic and endocrine regulations. J. Neurosci. 19, 1072–1087..
174. Horvath, T. L., and Gao, X. B. (2005). Input organization and plasticity of hypocretin neurons: possible clues to obesity’s association with insomnia. Cell Metab. 1, 279–286. doi: 10.1016/j.cmet.2005.03.003.
175. Horvath, T. L., Peyron, C., Diano, S., Ivanov, A., Aston-Jones, G., Kilduff, T. S., et al. (1999b). Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J. Comp. Neurol. 415, 145–159. doi: 10.1002/(sici)1096-9861(19991213)415:2<145::aid-cne1>3.3.co;2-u.
176. Hou, I. C., Suzuki, C., Kanegawa, N., Oda, A., Yamada, A., Yoshikawa, M. , et al. (2011). beta-Lactotensin derived from bovine beta-lactoglobulin exhibits anxiolytic-like activity as an agonist for neurotensin NTS(2) receptor via activation of dopamine D(1) receptor in mice. J. Neurochem. 119, 785–790. doi: 10.1111/j.1471-4159.2011.07472.x.
177. Huang, Z. L., Qu, W. M., Li, W. D., Mochizuki, T., Eguchi, N., Watanabe, T., et al. (2001). Arousal effect of orexin A depends on activation of the histaminergic system. Proc. Natl. Acad. Sci. U S A 98, 9965–9970. doi: 10.1073/pnas.181330998.
178. Hwang, J. R., Baek, M. W., Sim, J., Choi, H. S., Han, J. M., Kim, Y. L., et al. (2010). Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors. Biochem. Biophys. Res. Commun. 391, 1007–1013. doi: 10.1016/j.bbrc.2009.12.007.
179. Ida, T., Nakahara, K., Katayama, T., Murakami, N., and Nakazato, M. (1999). Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats. Brain Res. 821, 526–529. doi: 10.1016/s0006-8993(99)01131-2.
180. Iftene, F., Bowie, C., Milev, R., Hawken, E., Talikowska-Szymczak, E., Potopsingh, D., et al. (2013). Identification of primary polydipsia in a severe and persistent mental illness outpatient population: a prospective observational study. Psychiatry Res. 210, 679–683. doi: 10.1016/j.psychres.2013.04.011.
181. Inutsuka, A., Inui, A., Tabuchi, S., Tsunematsu, T., Lazarus, M., and Yamanaka, A. (2014). Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons. Neuropharmacology 85C, 451–460. doi: 10.1016/j.neuropharm.2014.06.015.
182. Iversen, L. L., Iversen, S. D., Bloom, F., Douglas, C., Brown, M., and Vale, W. (1978). Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro. Nature 273, 161–163. doi: 10.1038/273161a0.
183. Jego, S., Glasgow, S. D., Herrera, C. G., Ekstrand, M., Reed, S. J., Boyce, R., et al. (2013). Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat. Neurosci. 16, 1637–1643. doi: 10.1038/nn.3522.
184. Jensen, M. D., Ryan, D. H., Apovian, C. M., Ard, J. D., Comuzzie, A. G., Donato, K. A. , et al. (2014). 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129, S102–S138. doi: 10.1161/01.cir.0000437739.71477.ee.
185. Jeon, J. Y., Bradley, R. L., Kokkotou, E. G., Marino, F. E., Wang, X., Pissios, P., et al. (2006). MCH−/− mice are resistant to aging-associated increases in body weight and insulin resistance. Diabetes 55, 428–434. doi: 10.2337/diabetes.55.02.06.db05-0203.
186. Johnson, P. L., Samuels, B. C., Fitz, S. D., Lightman, S. L., Lowry, C. A., and Shekhar, A. (2012). Activation of the orexin 1 receptor is a critical component of CO2-mediated anxiety and hypertension but not bradycardia. Neuropsychopharmacology 37, 1911–1922. doi: 10.1038/npp.2012.38.
187. Johnson, P. L., Truitt, W., Fitz, S. D., Minick, P. E., Dietrich, A., Sanghani, S., et al. (2010). A key role for orexin in panic anxiety. Nat. Med. 16, 111–115. doi: 10.1038/nm.2075.
188. Jolicoeur, F. B., Rivest, R., St-Pierre, S., Gagné, M. A., and Dumais, M. (1985). The effects of neurotensin and [D-Tyr11]-NT on the hyperactivity induced by intra-accumbens administration of a potent dopamine receptor agonist. Neuropeptides 6, 143–156. doi: 10.1016/0143-4179(85)90105-2.
189. Kahn, D., Hou-Yu, A., and Zimmerman, E. A. (1982). Localization of neurotensin in the hypothalamus. Ann. N Y Acad. Sci. 400, 117–131. doi: 10.1111/j.1749-6632.1982.tb31564.x.
190. Kalivas, P. W., Burgess, S. K., Nemeroff, C. B., and Prange, A. J. Jr. (1983). Behavioral and neurochemical effects of neurotensin microinjection into the ventral tegmental area of the rat. Neuroscience 8, 495–505. doi: 10.1016/0306-4522(83)90195-1.
191. Kalivas, P. W., and Duffy, P. (1990). Effect of acute and daily neurotensin and enkephalin treatments on extracellular dopamine in the nucleus accumbens. J. Neurosci. 10, 2940–2949. doi: 10.1002/syn.890050104.
192. Kalivas, P. W., Jennes, L., and Miller, J. S. (1985a). A catecholaminergic projection from the ventral tegmental area to the diagonal band of Broca: modulation by neurotensin. Brain Res. 326, 229–238. doi: 10.1016/0006-8993(85)90032-0.
193. Kalivas, P. W., Nemeroff, C. B., and Prange, A. J. Jr. (1981). Increase in spontaneous motor activity following infusion of neurotensin into the ventral tegmental area. Brain Res. 229, 525–529. doi: 10.1016/0006-8993(81)91016-7.
194. Kalivas, P. W., Nemeroff, C. B., and Prange, A. J. Jr. (1982). Neuroanatomical sites of action of neurotensin. Ann. N Y Acad. Sci. 400, 307–318. doi: 10.1111/j.1749-6632.1982.tb31577.x.
195. Kalivas, P. W., Nemeroff, C. B., Miller, J. S., and Prange, A. J. Jr. (1985b). Microinjection of neurotensin into the ventral tegmental area produces hypothermia: evaluation of dopaminergic mediation. Brain Res. 326, 219–227. doi: 10.1016/0006-8993(85)90031-9.
196. Kalivas, P. W., and Taylor, S. (1985). Behavioral and neurochemical effect of daily injection with neurotensin into the ventral tegmental area. Brain Res. 358, 70–76. doi: 10.1016/0006-8993(85)90949-7.
197. Kantor, S., Mochizuki, T., Lops, S. N., Ko, B., Clain, E., Clark, E., et al. (2013). Orexin gene therapy restores the timing and maintenance of wakefulness in narcoleptic mice. Sleep 36, 1129–1138. doi: 10.5665/sleep.2870.
198. Karnani, M. M., Apergis-Schoute, J., Adamantidis, A., Jensen, L. T., De Lecea, L., Fugger, L., et al. (2011). Activation of central orexin/hypocretin neurons by dietary amino acids. Neuron 72, 616–629. doi: 10.1016/j.neuron.2011.08.027.
199. Karnani, M. M., Szabó, G., Erdélyi, F., and Burdakov, D. (2013). Lateral hypothalamic GAD65 neurons are spontaneously firing and distinct from orexin- and melanin-concentrating hormone neurons. J. Physiol. 591, 933–953. doi: 10.1113/jphysiol.2012.243493.
200. Kawai, Y., Takagi, H., and Tohyama, M. (1988). Co-localization of neurotensin- and cholecystokinin-like immunoreactivities in catecholamine neurons in the rat dorsomedial medulla. Neuroscience 24, 227–236. doi: 10.1016/0306-4522(88)90326-0.
201. Kawauchi, H., Kawazoe, I., Tsubokawa, M., Kishida, M., and Baker, B. I. (1983). Characterization of melanin-concentrating hormone in chum salmon pituitaries. Nature 305, 321–323. doi: 10.1038/305321a0.
202. Kaye, W. H., Wierenga, C. E., Bailer, U. F., Simmons, A. N., and Bischoff-Grethe, A. (2013). Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci. 36, 110–120. doi: 10.1016/j.tins.2013.01.003.
203. Kempadoo, K. A., Tourino, C., Cho, S. L., Magnani, F., Leinninger, G. M., Stuber, G. D., et al. (2013). Hypothalamic neurotensin projections promote reward by enhancing glutamate transmission in the VTA. J. Neurosci. 33, 7618–7626. doi: 10.1523/jneurosci.2588-12.2013.
204. Kenny, P. J. (2011). Reward mechanisms in obesity: new insights and future directions. Neuron 69, 664–679. doi: 10.1016/j.neuron.2011.02.016.
205. Kessler, J. P., Moyse, E., Kitabgi, P., Vincent, J. P., and Beaudet, A. (1987). Distribution of neurotensin binding sites in the caudal brainstem of the rat: a light microscopic radioautographic study. Neuroscience 23, 189–198. doi: 10.1016/0306-4522(87)90282-x.
206. Kessler, B. A., Stanley, E. M., Frederick-Duus, D., and Fadel, J. (2011). Age-related loss of orexin/hypocretin neurons. Neuroscience 178, 82–88. doi: 10.1016/j.neuroscience.2011.01.031.
207. Kim, E. R., Leckstrom, A., and Mizuno, T. M. (2008). Impaired anorectic effect of leptin in neurotensin receptor 1-deficient mice. Behav. Brain Res. 194, 66–71. doi: 10.1016/j.bbr.2008.06.024.
208. Kitabgi, P., Rostène, W., Dussaillant, M., Schotte, A., Laduron, P. M., and Vincent, J. P. (1987). Two populations of neurotensin binding sites in murine brain: discrimination by the antihistamine levocabastine reveals markedly different radioautographic distribution. Eur. J. Pharmacol. 140, 285–293. doi: 10.1016/0014-2999(87)90285-8.
209. Kiwaki, K., Kotz, C. M., Wang, C., Lanningham-Foster, L., and Levine, J. A. (2004). Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats. Am. J. Physiol. Endocrinol. Metab. 286, E551–559. doi: 10.1152/ajpendo.00126.2003.
210. Kleczkowska, P., and Lipkowski, A. W. (2013). Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation–a review. Eur. J. Pharmacol. 716, 54–60. doi: 10.1016/j.ejphar.2013.03.004.
211. Konadhode, R. R., Pelluru, D., Blanco-Centurion, C., Zayachkivsky, A., Liu, M., Uhde, T., et al. (2013). Optogenetic stimulation of MCH neurons increases sleep. J. Neurosci. 33, 10257–10263. doi: 10.1523/jneurosci.1225-13.2013.
212. Kong, D., Vong, L., Parton, L. E., Ye, C., Tong, Q., Hu, X., et al. (2010). Glucose stimulation of hypothalamic MCH neurons involves K(ATP) channels, is modulated by UCP2 and regulates peripheral glucose homeostasis. Cell Metab. 12, 545–552. doi: 10.1016/j.cmet.2010.09.013.
213. Korotkova, T. M., Sergeeva, O. A., Eriksson, K. S., Haas, H. L., and Brown, R. E. (2003). Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J. Neurosci. 23, 7–11..
214. Kotz, C. M., Wang, C., Teske, J. A., Thorpe, A. J., Novak, C. M., Kiwaki, K., et al. (2006). Orexin A mediation of time spent moving in rats: neural mechanisms. Neuroscience 142, 29–36. doi: 10.1016/j.neuroscience.2006.05.028.
215. Kowalski, T. J., Farley, C., Cohen-Williams, M. E., Varty, G., and Spar, B. D. (2004). Melanin-concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size. Eur. J. Pharmacol. 497, 41–47. doi: 10.1016/j.ejphar.2004.06.027.
216. Kowalski, T. J., Spar, B. D., Weig, B., Farley, C., Cook, J., Ghibaudi, L., et al. (2006). Effects of a selective melanin-concentrating hormone 1 receptor antagonist on food intake and energy homeostasis in diet-induced obese mice. Eur. J. Pharmacol. 535, 182–191. doi: 10.1016/j.ejphar.2006.01.062.
217. Kunii, K., Yamanaka, A., Nambu, T., Matsuzaki, I., Goto, K., and Sakurai, T. (1999). Orexins/hypocretins regulate drinking behaviour. Brain Res. 842, 256–261. doi: 10.1016/s0006-8993(99)01884-3.
218. Lagos, P., Torterolo, P., Jantos, H., Chase, M. H., and Monti, J. M. (2009). Effects on sleep of melanin-concentrating hormone (MCH) microinjections into the dorsal raphe nucleus. Brain Res. 1265, 103–110. doi: 10.1016/j.brainres.2009.02.010.
219. Laque, A., Zhang, Y., Gettys, S., Nguyen, T. A., Bui, K., Morrison, C. D., et al. (2013). Leptin receptor neurons in the mouse hypothalamus are co-localized with the neuropeptide galanin and mediate anorexigenic leptin action. Am. J. Physiol. Endocrinol. Metab. 304, E999–E1011. doi: 10.1152/ajpendo.00643.2012.
220. Lawrence, C. B., Snape, A. C., Baudoin, F. M., and Luckman, S. M. (2002). Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 143, 155–162. doi: 10.1210/en.143.1.155.
221. Lee, M. G., Hassani, O. K., and Jones, B. E. (2005). Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J. Neurosci. 25, 6716–6720. doi: 10.1523/jneurosci.1887-05.2005.
222. Lee, M. R., Hinton, D. J., Song, J. Y., Lee, K. W., Choo, C., Johng, H., et al. (2010). Neurotensin receptor type 1 regulates ethanol intoxication and consumption in mice. Pharmacol. Biochem. Behav. 95, 235–241. doi: 10.1016/j.pbb.2010.01.012.
223. Lee, M. R., Hinton, D. J., Unal, S. S., Richelson, E., and Choi, D. S. (2011). Increased ethanol consumption and preference in mice lacking neurotensin receptor type 2. Alcohol. Clin. Exp. Res. 35, 99–107. doi: 10.1111/j.1530-0277.2010.01326.x.
224. Lee, S. J., Kirigiti, M., Lindsley, S. R., Loche, A., Madden, C. J., Morrison, S. F., et al. (2013). Efferent projections of neuropeptide Y-expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models. J. Comp. Neurol. 521, 1891–1914. doi: 10.1002/cne.23265.
225. Lee, Y. C., Uttenthal, L. O., Smith, H. A., and Bloom, S. R. (1986). In vitro degradation of neurotensin in human plasma. Peptides 7, 383–387. doi: 10.1016/0196-9781(86)90002-1.
226. Legault, M., Congar, P., Michel, F. J., and Trudeau, L. E. (2002). Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic neurones. Neuroscience 111, 177–187. doi: 10.1016/s0306-4522(01)00614-5.
227. Leinninger, G. M., Jo, Y. H., Leshan, R. L., Louis, G. W., Yang, H., Barrera, J. G., et al. (2009). Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 10, 89–98. doi: 10.1016/j.cmet.2009.06.011.
228. Leinninger, G. M., Opland, D. M., Jo, Y. H., Faouzi, M., Christensen, L., Cappellucci, L. A., et al. (2011). Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 14, 313–323. doi: 10.1016/j.cmet.2011.06.016.
229. Lembo, P. M., Grazzini, E., Cao, J., Hubatsch, D. A., Pelletier, M., Hoffert, C., et al. (1999). The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor. Nat. Cell Biol. 1, 267–271..
230. Levitt, D. R., and Teitelbaum, P. (1975). Somnolence, akinesia and sensory activation of motivated behavior in the lateral hypothalamic syndrome. Proc. Natl. Acad. Sci. U S A 72, 2819–2823. doi: 10.1073/pnas.72.7.2819.
231. Li, Y., Gao, X. B., Sakurai, T., and van den Pol, A. N. (2002). Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system. Neuron 36, 1169–1181. doi: 10.1016/s0896-6273(02)01132-7.
232. Li, Y., and van den Pol, A. N. (2006). Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. J. Neurosci. 26, 13037–13047. doi: 10.1523/jneurosci.3380-06.2006.
233. Liu, M., Thankachan, S., Kaur, S., Begum, S., Blanco-Centurion, C., Sakurai, T., et al. (2008). Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice. Eur J. Neurosci. 28, 1382–1393. doi: 10.1111/j.1460-9568.2008.06446.x.
234. Look, A. R. G., Wing, R. R., Bolin, P., Brancati, F. L., Bray, G. A., Clark, J. M., et al. (2013). Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N. Engl. J. Med. 369, 145–154. doi: 10.1056/NEJMoa1212914.
235. Louis, G. W., Leinninger, G. M., Rhodes, C. J., and Myers, M. G. Jr. (2010). Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons. J. Neurosci. 30, 11278–11287. doi: 10.1523/jneurosci.1340-10.2010.
236. Lu, B., Su, Y., Das, S., Wang, H., Wang, Y., Liu, J., et al. (2009). Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature 457, 741–744. doi: 10.1038/nature07579.
237. Ludwig, D. S., Tritos, N. A., Mastaitis, J. W., Kulkarni, R., Kokkotou, E., Elmquist, J., et al. (2001). Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J. Clin. Invest. 107, 379–386. doi: 10.1172/jci10660.
238. Lutter, M., Krishnan, V., Russo, S. J., Jung, S., Mcclung, C. A., and Nestler, E. J. (2008). Orexin signaling mediates the antidepressant-like effect of calorie restriction. J. Neurosci. 28, 3071–3075. doi: 10.1523/jneurosci.5584-07.2008.
239. Mahler, S. V., Smith, R. J., and Aston-Jones, G. (2013). Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl) 226, 687–698. doi: 10.1007/s00213-012-2681-5.
240. Marsh, D. J., Weingarth, D. T., Novi, D. E., Chen, H. Y., Trumbauer, M. E., Chen, A. S., et al. (2002). Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive and hyperphagic and have altered metabolism. Proc. Natl. Acad. Sci. U S A 99, 3240–3245. doi: 10.1073/pnas.052706899.
241. Marshall, J. F., and Teitelbaum, P. (1973). A comparison of the eating in response to hypothermic and glucoprivic challenges after nigral 6-hydroxydopamine and lateral hypothalamic electrolytic lesions in rats. Brain Res. 55, 229–233. doi: 10.1016/0006-8993(73)90507-6.
242. Martin, G. E., Bacino, C. B., and Papp, N. L. (1980). Hypothermia elicited by the intracerebral microinjection of neurotensin. Peptides 1, 333–339. doi: 10.1016/0196-9781(80)90011-x.
243. Martin, G., Fabre, V., Siggins, G. R., and De Lecea, L. (2002). Interaction of the hypocretins with neurotransmitters in the nucleus accumbens. Regul. Pept. 104, 111–117. doi: 10.1016/s0167-0115(01)00354-8.
244. Matsuki, T., Nomiyama, M., Takahira, H., Hirashima, N., Kunita, S., Takahashi, S., et al. (2009). Selective loss of GABA(B) receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc. Natl. Acad. Sci. U S A 106, 4459–4464. doi: 10.1073/pnas.0811126106.
245. Matsuo, E., Mochizuki, A., Nakayama, K., Nakamura, S., Yamamoto, T., Shioda, S., et al. (2010). Decreased intake of sucrose solutions in orexin knockout mice. J. Mol. Neurosci. 43, 217–224. doi: 10.1007/s12031-010-9475-1.
246. Mazella, J., Botto, J. M., Guillemare, E., Coppola, T., Sarret, P., and Vincent, J. P. (1996). Structure, functional expression and cerebral localization of the levocabastine-sensitive neurotensin/neuromedin N receptor from mouse brain. J. Neurosci. 16, 5613–5620..
247. Mazella, J., Kitabgi, P., and Vincent, J. P. (1985). Molecular properties of neurotensin receptors in rat brain. Identification of subunits by covalent labeling. J. Biol. Chem. 260, 508–514. doi: 10.1016/0196-9781(85)90440-1.
248. Mazella, J., Zsürger, N., Navarro, V., Chabry, J., Kaghad, M., Caput, D., et al. (1998). The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. J. Biol. Chem. 273, 26273–26276. doi: 10.1074/jbc.273.41.26273.
249. McDermott, J. R., Virmani, M. A., Turner, J. D., and Kidd, A. M. (1986). Peptidases involved in the catabolism of neurotensin: inhibitor studies using superfused rat hypothalamic slices. Peptides 7, 225–230. doi: 10.1016/0196-9781(86)90217-2.
250. McGregor, R., Wu, M. F., Barber, G., Ramanathan, L., and Siegel, J. M. (2011). Highly specific role of hypocretin (orexin) neurons: differential activation as a function of diurnal phase, operant reinforcement versus operant avoidance and light level. J. Neurosci. 31, 15455–15467. doi: 10.1523/JNEUROSCI.4017-11.2011.
251. Meerabux, J., Iwayama, Y., Sakurai, T., Ohba, H., Toyota, T., Yamada, K., et al. (2005). Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. Biol. Psychiatry 58, 401–407. doi: 10.1016/j.biopsych.2005.04.015.
252. Meguid, M. M., Glade, M. J., and Middleton, F. A. (2008). Weight regain after Roux-en-Y: a significant 20% complication related to PYY. Nutrition 24, 832–842. doi: 10.1016/j.nut.2008.06.027.
253. Mieda, M., Hasegawa, E., Kisanuki, Y. Y., Sinton, C. M., Yanagisawa, M., and Sakurai, T. (2011). Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J. Neurosci. 31, 6518–6526. doi: 10.1523/JNEUROSCI.6506-10.2011.
254. Mieda, M., Williams, S. C., Sinton, C. M., Richardson, J. A., Sakurai, T., and Yanagisawa, M. (2004). Orexin neurons function in an efferent pathway of a food-entrainable circadian oscillator in eliciting food-anticipatory activity and wakefulness. J. Neurosci. 24, 10493–10501. doi: 10.1523/jneurosci.3171-04.2004.
255. Milella, M. S., Passarelli, F., De Carolis, L., Schepisi, C., Nativio, P., Scaccianoce, S., et al. (2010). Opposite roles of dopamine and orexin in quinpirole-induced excessive drinking: a rat model of psychotic polydipsia. Psychopharmacology (Berl) 211, 355–366. doi: 10.1007/s00213-010-1909-5.
256. Mileykovskiy, B. Y., Kiyashchenko, L. I., and Siegel, J. M. (2005). Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46, 787–798. doi: 10.1016/j.neuron.2005.04.035.
257. Mochizuki, T., Arrigoni, E., Marcus, J. N., Clark, E. L., Yamamoto, M., Honer, M., et al. (2011). Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice. Proc. Natl. Acad. Sci. U S A 108, 4471–4476. doi: 10.1073/pnas.1012456108.
258. Mochizuki, T., Crocker, A., Mccormack, S., Yanagisawa, M., Sakurai, T., and Scammell, T. E. (2004). Behavioral state instability in orexin knock-out mice. J. Neurosci. 24, 6291–6300. doi: 10.1523/jneurosci.0586-04.2004.
259. Moga, M. M., Saper, C. B., and Gray, T. S. (1990). Neuropeptide organization of the hypothalamic projection to the parabrachial nucleus in the rat. J. Comp. Neurol. 295, 662–682. doi: 10.1002/cne.902950409.
260. Mogenson, G. J., and Morgan, C. W. (1967). Effects of induced drinking on self-stimulation of the lateral hypothalamus. Exp. Brain Res. 3, 111–116..
261. Mogenson, G. J., and Stevenson, J. A. (1967). Drinking induced by electrical stimulation of the lateral hypothalamus. Exp. Neurol. 17, 119–127. doi: 10.1016/0014-4886(67)90139-2.
262. Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., et al. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903–908..
263. Morgane, P. J. (1961). Distinct “feeding” and “hunger motivating” systems in the lateral hypothalamus of the rat. Science 133, 887–888. doi: 10.1126/science.133.3456.887.
264. Morrison, S. D., Barrnett, R. J., and Mayer, J. (1958). Localization of lesions in the lateral hypothalamus of rats with induced adipsia and aphagia. Am. J. Physiol. 193, 230–234..
265. Mouri, T., Takahashi, K., Kawauchi, H., Sone, M., Totsune, K., Murakami, O., et al. (1993). Melanin-concentrating hormone in the human brain. Peptides 14, 643–646. doi: 10.1016/0196-9781(93)90158-d.
266. Moyse, E., Rostene, W., Vial, M., Leonard, K., Mazella, J., Kitabgi, P., et al. (1987). Distribution of neurotensin binding sites in rat brain: a light microscopic radioautographic study using monoiodo [125I]Tyr3-neurotensin. Neuroscience 22, 525–536. doi: 10.1016/0306-4522(87)90350-2.
267. Muschamp, J. W., Hollander, J. A., Thompson, J. L., Voren, G., Hassinger, L. C., Onvani, S., et al. (2014). Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area. Proc. Natl. Acad. Sci. U S A 111, E1648–E1655. doi: 10.1073/pnas.1315542111.
268. Myers, M. G. Jr., Münzberg, H., Leinninger, G. M., and Leshan, R. L. (2009). The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metab. 9, 117–123. doi: 10.1016/j.cmet.2008.12.001.
269. Najimi, M., Sarrieau, A., Kopp, N., and Chigr, F. (2014). An autoradiographic study of neurotensin receptors in the human hypothalamus. Acta Histochem. 116, 382–389. doi: 10.1016/j.acthis.2013.09.008.
270. Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., et al. (2001). A role for ghrelin in the central regulation of feeding. Nature 409, 194–198. doi: 10.1038/35051587.
271. Nalivaiko, E., Michaud, J. C., Soubrié, P., and Le Fur, G. (1998). Electrophysiological evidence for putative subtypes of neurotensin receptors in guinea-pig mesencephalic dopaminergic neurons. Neuroscience 86, 799–811. doi: 10.1016/s0306-4522(98)00084-0.
272. Narita, M., Nagumo, Y., Hashimoto, S., Narita, M., Khotib, J., Miyatake, M., et al. (2006). Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. J. Neurosci. 26, 398–405. doi: 10.1523/jneurosci.2761-05.2006.
273. Nemeroff, C. B., Bissette, G., Prange, A. J. Jr., Loosen, P. T., Barlow, T. S., and Lipton, M. A. (1977). Neurotensin: central nervous system effects of a hypothalamic peptide. Brain Res. 128, 485–496. doi: 10.1016/0006-8993(77)90173-1.
274. Nemeroff, C. B., Hernandez, D. E., Luttinger, D., Kalivas, P. W., and Prange, A. J. Jr. (1982). Interactions of neurotensin with brain dopamine systems. Ann. N Y Acad. Sci. 400, 330–344. doi: 10.1111/j.1749-6632.1982.tb31579.x.
275. Nishino, S., Ripley, B., Overeem, S., Lammers, G. J., and Mignot, E. (2000). Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355, 39–40. doi: 10.1016/s0140-6736(99)05582-8.
276. Nishino, S., Ripley, B., Overeem, S., Nevsimalova, S., Lammers, G. J., Vankova, J., et al. (2001). Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy. Ann. Neurol. 50, 381–388. doi: 10.1002/ana.1130.
277. Nogueiras, R., Tschöp, M. H., and Zigman, J. M. (2008). Central nervous system regulation of energy metabolism: ghrelin versus leptin. Ann. N Y Acad. Sci. 1126, 14–19. doi: 10.1196/annals.1433.054.
278. Nouel, D., Faure, M. P., St Pierre, J. A., Alonso, R., Quirion, R., and Beaudet, A. (1997). Differential binding profile and internalization process of neurotensin via neuronal and glial receptors. J. Neurosci. 17, 1795–1803..
279. Nouel, D., Sarret, P., Vincent, J. P., Mazella, J., and Beaudet, A. (1999). Pharmacological, molecular and functional characterization of glial neurotensin receptors. Neuroscience 94, 1189–1197. doi: 10.1196/annals.1433.054.
280. Obici, S., Zhang, B. B., Karkanias, G., and Rossetti, L. (2002). Hypothalamic insulin signaling is required for inhibition of glucose production. Nat. Med. 8, 1376–1382. doi: 10.1038/nm1202-798.
281. Oldfield, B. J., Allen, A. M., Davern, P., Giles, M. E., and Owens, N. C. (2007). Lateral hypothalamic’command neurons’ with axonal projections to regions involved in both feeding and thermogenesis. Eur J. Neurosci. 25, 2404–2412. doi: 10.1111/j.1460-9568.2007.05429.x.
282. Oldfield, B. J., Giles, M. E., Watson, A., Anderson, C., Colvill, L. M., and Mckinley, M. J. (2002). The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat. Neuroscience 110, 515–526. doi: 10.1016/s0306-4522(01)00555-3.
283. Olszewski, P. K., Li, D., Grace, M. K., Billington, C. J., Kotz, C. M., and Levine, A. S. (2003). Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus. Peptides 24, 597–602. doi: 10.1016/s0196-9781(03)00105-0.
284. Ono, K., Kai, A., Honda, E., and Inenaga, K. (2008). Hypocretin-1/orexin-A activates subfornical organ neurons of rats. Neuroreport 19, 69–73. doi: 10.1097/wnr.0b013e3282f32d64.
285. Opland, D., Sutton, S. A., Woodworth, H., Brown, J., Bugescu, R., Garcia, A., et al. (2013). Loss of neurotensin receptor-1 disrupts the control of the mesolimbic dopamine system by leptin and promotes hedonic feeding and obesity. Mol. Metab. 2, 423–434. doi: 10.1016/j.molmet.2013.07.008.
286. Osbahr, A. J. 3rd, Nemeroff, C. B., Luttinger, D., Mason, G. A., and Prange, A. J. Jr. (1981). Neurotensin-induced antinociception in mice: antagonism by thyrotropin-releasing hormone. J. Pharmacol. Exp. Ther. 217, 645–651..
287. Oshima, N., Kasukawa, H., Fujii, R., Wilkes, B. C., Hruby, V. J., and Hadley, M. E. (1986). Action of melanin-concentrating hormone (MCH) on teleost chromatophores. Gen. Comp. Endocrinol. 64, 381–388. doi: 10.1016/0016-6480(86)90072-9.
288. Pankevich, D. E., Teegarden, S. L., Hedin, A. D., Jensen, C. L., and Bale, T. L. (2010). Caloric restriction experience reprograms stress and orexigenic pathways and promotes binge eating. J. Neurosci. 30, 16399–16407. doi: 10.1523/jneurosci.1955-10.2010.
289. Park, S. M., Gaykema, R. P., and Goehler, L. E. (2008). How does immune challenge inhibit ingestion of palatable food? Evidence that systemic lipopolysaccharide treatment modulates key nodal points of feeding neurocircuitry. Brain Behav. Immun. 22, 1160–1172. doi: 10.1016/j.bbi.2008.05.001.
290. Parks, G. S., Olivas, N. D., Ikrar, T., Sanathara, N. M., Wang, L., Wang, Z., et al. (2014). Histamine inhibits the melanin-concentrating hormone system: implications for sleep and arousal. J. Physiol. 592, 2183–2196. doi: 10.1113/jphysiol.2013.268771.
291. Paxinos, G., and Franklin, B. (2001). The Mouse Brain in Stereotaxic Coordinates. 2nd Edn. Academic Press..
292. Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., et al. (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543. doi: 10.1126/science.7624776.
293. Pereira-Da-Silva, M., Torsoni, M. A., Nourani, H. V., Augusto, V. D., Souza, C. T., Gasparetti, A. L., et al. (2003). Hypothalamic melanin-concentrating hormone is induced by cold exposure and participates in the control of energy expenditure in rats. Endocrinology 144, 4831–4840. doi: 10.1210/en.2003-0243.
294. Perello, M., Sakata, I., Birnbaum, S., Chuang, J. C., Osborne-Lawrence, S., Rovinsky, S. A., et al. (2010). Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol. Psychiatry 67, 880–886. doi: 10.1016/j.biopsych.2009.10.030.
295. Petrovich, G. D., Hobin, M. P., and Reppucci, C. J. (2012). Selective Fos induction in hypothalamic orexin/hypocretin, but not melanin-concentrating hormone neurons, by a learned food-cue that stimulates feeding in sated rats. Neuroscience 224, 70–80. doi: 10.1016/j.neuroscience.2012.08.036.
296. Pettibone, D. J., Hess, J. F., Hey, P. J., Jacobson, M. A., Leviten, M., Lis, E. V., et al. (2002). The effects of deleting the mouse neurotensin receptor NTR1 on central and peripheral responses to neurotensin. J. Pharmacol. Exp. Ther. 300, 305–313. doi: 10.1124/jpet.300.1.305.
297. Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., et al. (2000). A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat. Med. 6, 991–997. doi: 10.1038/79690.
298. Peyron, C., Tighe, D. K., van den Pol, A. N., De Lecea, L., Heller, H. C., Sutcliffe, J. G., et al. (1998). Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18, 9996–10015..
299. Pissios, P., Frank, L., Kennedy, A. R., Porter, D. R., Marino, F. E., Liu, F. F., et al. (2008). Dysregulation of the mesolimbic dopamine system and reward in MCH−/− mice. Biol. Psychiatry 64, 184–191. doi: 10.1016/j.biopsych.2007.12.011.
300. Pissios, P., Trombly, D. J., Tzameli, I., and Maratos-Flier, E. (2003). Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways. Endocrinology 144, 3514–3523. doi: 10.1210/en.2002-0004.
301. Poli, F., Plazzi, G., Di Dalmazi, G., Ribichini, D., Vicennati, V., Pizza, F., et al. (2009). Body mass index-independent metabolic alterations in narcolepsy with cataplexy. Sleep 32, 1491–1497..
302. Popp, E., Schneider, A., Vogel, P., Teschendorf, P., and Bottiger, B. W. (2007). Time course of the hypothermic response to continuously administered neurotensin. Neuropeptides 41, 349–354. doi: 10.1016/j.npep.2007.06.002.
303. Pozza, M. F., Kung, E., Bischoff, S., and Olpe, H. R. (1988). The neurotensin analog xenopsin excites nigral dopamine neurons. Eur. J. Pharmacol. 145, 341–343. doi: 10.1016/0014-2999(88)90439-6.
304. Qu, D., Ludwig, D. S., Gammeltoft, S., Piper, M., Pelleymounter, M. A., Cullen, M. J., et al. (1996). A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature 380, 243–247. doi: 10.1038/380243a0.
305. Quirk, W. S., Wright, J. W., and Harding, J. W. (1988). Tachyphylaxis of dipsogenic activity to intracerebroventricular administration of angiotensins. Brain Res. 452, 73–78. doi: 10.1016/0006-8993(88)90010-8.
306. Rai, S., Kumar, S., Alam, M. A., Szymusiak, R., Mcginty, D., and Alam, M. N. (2010). A1 receptor mediated adenosinergic regulation of perifornical-lateral hypothalamic area neurons in freely behaving rats. Neuroscience 167, 40–48. doi: 10.1016/j.neuroscience.2010.01.044.
307. Ramanjaneya, M., Conner, A. C., Chen, J., Kumar, P., Brown, J. E., Johren, O., et al. (2009). Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B. J. Endocrinol. 202, 249–261. doi: 10.1677/joe-08-0536.
308. Ranson, S. W. (1937). Some functions of the hypothalamus: Harvey Lecture, December 17, 1936. Bull. N Y Acad. Med. 13, 241–271..
309. Rao, Y., Liu, Z. W., Borok, E., Rabenstein, R. L., Shanabrough, M., Lu, M., et al. (2007). Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. J. Clin. Invest. 117, 4022–4033. doi: 10.1172/jci32829.
310. Rao, Y., Lu, M., Ge, F., Marsh, D. J., Qian, S., Wang, A. H., et al. (2008). Regulation of synaptic efficacy in hypocretin/orexin-containing neurons by melanin concentrating hormone in the lateral hypothalamus. J. Neurosci. 28, 9101–9110. doi: 10.1523/jneurosci.1766-08.2008.
311. Remaury, A., Vita, N., Gendreau, S., Jung, M., Arnone, M., Poncelet, M., et al. (2002). Targeted inactivation of the neurotensin type 1 receptor reveals its role in body temperature control and feeding behavior but not in analgesia. Brain Res. 953, 63–72. doi: 10.1016/s0006-8993(02)03271-7.
312. Reti, I. M., Reddy, R., Worley, P. F., and Baraban, J. M. (2002). Selective expression of Narp, a secreted neuronal pentraxin, in orexin neurons. J. Neurochem. 82, 1561–1565. doi: 10.1046/j.1471-4159.2002.01141.x.
313. Richardson, K. A., and Aston-Jones, G. (2012). Lateral hypothalamic orexin/hypocretin neurons that project to ventral tegmental area are differentially activated with morphine preference. J. Neurosci. 32, 3809–3817. doi: 10.1523/jneurosci.3917-11.2012.
314. Richy, S., Burlet, A., Max, J., Burlet, C., and Beck, B. (2000). Effect of chronic intraperitoneal injections of leptin on hypothalamic neurotensin content and food intake. Brain Res. 862, 276–279. doi: 10.1016/s0006-8993(00)02125-9.
315. Roberts, G. W., Woodhams, P. L., Polak, J. M., and Crow, T. J. (1984). Distribution of neuropeptides in the limbic system of the rat: the hippocampus. Neuroscience 11, 35–77. doi: 10.1016/0306-4522(84)90214-8.
316. Rodgers, R. J., Halford, J. C., Nunes De Souza, R. L., Canto De Souza, A. L., Piper, D. C., Arch, J. R., et al. (2001). SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats. Eur J. Neurosci. 13, 1444–1452. doi: 10.1046/j.0953-816x.2001.01518.x.
317. Rodriguez, M., Beauverger, P., Naime, I., Rique, H., Ouvry, C., Souchaud, S., et al. (2001). Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2. Mol. Pharmacol. 60, 632–639..
318. Rolls, A., Colas, D., Adamantidis, A., Carter, M., Lanre-Amos, T., Heller, H. C., et al. (2011). Optogenetic disruption of sleep continuity impairs memory consolidation. Proc. Natl. Acad. Sci. U S A 108, 13305–13310. doi: 10.1073/pnas.1015633108.
319. Rosin, D. L., Weston, M. C., Sevigny, C. P., Stornetta, R. L., and Guyenet, P. G. (2003). Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2. J. Comp. Neurol. 465, 593–603. doi: 10.1002/cne.10860.
320. Rossi, M., Choi, S. J., O’shea, D., Miyoshi, T., Ghatei, M. A., and Bloom, S. R. (1997). Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight. Endocrinology 138, 351–355. doi: 10.1210/en.138.1.351.
321. Rovere, C., Barbero, P., and Kitabgi, P. (1996a). Evidence that PC2 is the endogenous pro-neurotensin convertase in rMTC 6–23 cells and that PC1- and PC2-transfected PC12 cells differentially process pro-neurotensin. J. Biol. Chem. 271, 11368–11375. doi: 10.1074/jbc.271.19.11368.
322. Rovere, C., Viale, A., Nahon, J., and Kitabgi, P. (1996b). Impaired processing of brain proneurotensin and promelanin-concentrating hormone in obese fat/fat mice. Endocrinology 137, 2954–2958. doi: 10.1210/en.137.7.2954.
323. Sahu, A. (1998). Evidence suggesting that galanin (GAL), melanin-concentrating hormone (MCH), neurotensin (NT), proopiomelanocortin (POMC) and neuropeptide Y (NPY) are targets of leptin signaling in the hypothalamus. Endocrinology 139, 795–798. doi: 10.1210/endo.139.2.5909.
324. Sahu, A., Carraway, R. E., and Wang, Y. P. (2001). Evidence that neurotensin mediates the central effect of leptin on food intake in rat. Brain Res. 888, 343–347. doi: 10.1016/s0006-8993(00)03107-3.
325. Saito, Y., Nothacker, H. P., Wang, Z., Lin, S. H., Leslie, F., and Civelli, O. (1999). Molecular characterization of the melanin-concentrating-hormone receptor. Nature 400, 265–269..
326. Sakamaki, R., Uemoto, M., Inui, A., Asakawa, A., Ueno, N., Ishibashi, C., et al. (2005). Melanin-concentrating hormone enhances sucrose intake. Int. J. Mol. Med. 15, 1033–1039. doi: 10.3892/ijmm.15.6.1033.
327. Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., et al. (1998). Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–585. doi: 10.1016/s0092-8674(00)80949-6.
328. Sandoval, S. L., and Kulkosky, P. J. (1992). Effects of peripheral neurotensin on behavior of the rat. Pharmacol. Biochem. Behav. 41, 385–390. doi: 10.1016/0091-3057(92)90115-v.
329. Sapin, E., Bérod, A., Léger, L., Herman, P. A., Luppi, P. H., and Peyron, C. (2010). A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM) sleep hypersomnia. PLoS One 5:e11766. doi: 10.1371/journal.pone.0011766.
330. Schone, C., Cao, Z. F., Apergis-Schoute, J., Adamantidis, A., Sakurai, T., and Burdakov, D. (2012). Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to histamine neurons in situ. J. Neurosci. 32, 12437–12443. doi: 10.1523/jneurosci.0706-12.2012.
331. Schöne, C., Venner, A., Knowles, D., Karnani, M. M., and Burdakov, D. (2011). Dichotomous cellular properties of mouse orexin/hypocretin neurons. J. Physiol. 589, 2767–2779. doi: 10.1113/jphysiol.2011.208637.
332. Schuld, A., Hebebrand, J., Geller, F., and Pollmacher, T. (2000). Increased body-mass index in patients with narcolepsy. Lancet 355, 1274–1275. doi: 10.1016/s0140-6736(05)74704-8.
333. Schwartz, M. W., Bergman, R. N., Kahn, S. E., Taborsky, G. J. Jr., Fisher, L. D., Sipols, A. J., et al. (1991). Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport. J. Clin. Invest. 88, 1272–1281. doi: 10.1172/jci115431.
334. Scott, M. M., Marcus, J. N., Pettersen, A., Birnbaum, S. G., Mochizuki, T., Scammell, T. E., et al. (2011). Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav. Brain Res. 222, 289–294. doi: 10.1016/j.bbr.2011.02.044.
335. Sears, R. M., Liu, R. J., Narayanan, N. S., Sharf, R., Yeckel, M. F., Laubach, M., et al. (2010). Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. J. Neurosci. 30, 8263–8273. doi: 10.1523/jneurosci.5858-09.2010.
336. Segal-Lieberman, G., Bradley, R. L., Kokkotou, E., Carlson, M., Trombly, D. J., Wang, X., et al. (2003). Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc. Natl. Acad. Sci. U S A 100, 10085–10090. doi: 10.1073/pnas.1633636100.
337. Sellayah, D., Bharaj, P., and Sikder, D. (2011). Orexin is required for brown adipose tissue development, differentiation and function. Cell Metab. 14, 478–490. doi: 10.1016/j.cmet.2011.08.010.
338. Sergeeva, O. A., Andreeva, N., Garret, M., Scherer, A., and Haas, H. L. (2005). Pharmacological properties of GABAA receptors in rat hypothalamic neurons expressing the epsilon-subunit. J. Neurosci. 25, 88–95. doi: 10.1523/jneurosci.3209-04.2005.
339. Seta, K. A., Jansen, H. T., Kreitel, K. D., Lehman, M., and Behbehani, M. M. (2001). Cold water swim stress increases the expression of neurotensin mRNA in the lateral hypothalamus and medial preoptic regions of the rat brain. Brain Res. Mol. Brain Res. 86, 145–152. doi: 10.1016/s0169-328x(00)00279-5.
340. Seutin, V., Massotte, L., and Dresse, A. (1989). Electrophysiological effects of neurotensin on dopaminergic neurones of the ventral tegmental area of the rat in vitro. Neuropharmacology 28, 949–954. doi: 10.1016/0028-3908(89)90194-9.
341. Sharf, R., Sarhan, M., Brayton, C. E., Guarnieri, D. J., Taylor, J. R., and Dileone, R. J. (2010). Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement. Biol. Psychiatry 67, 753–760. doi: 10.1016/j.biopsych.2009.12.035.
342. Sheng, Z., Santiago, A. M., Thomas, M. P., and Routh, V. H. (2014). Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry. Mol. Cell. Neurosci. 62, 30–41. doi: 10.1016/j.mcn.2014.08.001.
343. Sheppard, M. C., Bailey, C. J., Flatt, P. R., Swanston-Flatt, S. K., and Shennan, K. I. (1985). Immunoreactive neurotensin in spontaneous syndromes of obesity and diabetes in mice. Acta Endocrinol. (Copenh) 108, 532–536. doi: 10.1530/acta.0.1080532.
344. Sherwood, A., Wosiski-Kuhn, M., Nguyen, T., Holland, P. C., Lakaye, B., Adamantidis, A., et al. (2012). The role of melanin-concentrating hormone in conditioned reward learning. Eur J. Neurosci. 36, 3126–3133. doi: 10.1111/j.1460-9568.2012.08207.x.
345. Shi, W. X., and Bunney, B. S. (1991). Neurotensin modulates autoreceptor mediated dopamine effects on midbrain dopamine cell activity. Brain Res. 543, 315–321. doi: 10.1016/0006-8993(91)90043-u.
346. Shimada, M., Tritos, N. A., Lowell, B. B., Flier, J. S., and Maratos-Flier, E. (1998). Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396, 670–674..
347. Shipley, M. T., Mclean, J. H., and Behbehani, M. M. (1987). Heterogeneous distribution of neurotensin-like immunoreactive neurons and fibers in the midbrain periaqueductal gray of the rat. J. Neurosci. 7, 2025–2034..
348. Shirasaka, T., Nakazato, M., Matsukura, S., Takasaki, M., and Kannan, H. (1999). Sympathetic and cardiovascular actions of orexins in conscious rats. Am. J. Physiol. 277, R1780–R1785..
349. Shiuchi, T., Haque, M. S., Okamoto, S., Inoue, T., Kageyama, H., Lee, S., et al. (2009). Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab. 10, 466–480. doi: 10.1016/j.cmet.2009.09.013.
350. Singh, J., Desiraju, T., and Raju, T. R. (1997). Effects of microinjections of cholecystokinin and neurotensin into lateral hypothalamus and ventral mesencephalon on intracranial self-stimulation. Pharmacol. Biochem. Behav. 58, 893–898. doi: 10.1016/s0091-3057(97)00040-3.
351. Skoog, K. M., Cain, S. T., and Nemeroff, C. B. (1986). Centrally administered neurotensin suppresses locomotor hyperactivity induced by d-amphetamine but not by scopolamine or caffeine. Neuropharmacology 25, 777–782. doi: 10.1016/0028-3908(86)90095-x.
352. Smink, F. R., van Hoeken, D., and Hoek, H. W. (2012). Epidemiology of eating disorders: incidence, prevalence and mortality rates. Curr. Psychiatry Rep. 14, 406–414. doi: 10.1007/s11920-012-0282-y.
353. Smith, R. J., and Aston-Jones, G. (2012). Orexin/hypocretin 1 receptor antagonist reduces heroin self-administration and cue-induced heroin seeking. Eur J. Neurosci. 35, 798–804. doi: 10.1111/j.1460-9568.2012.08013.x.
354. Smith, D. G., Davis, R. J., Rorick-Kehn, L., Morin, M., Witkin, J. M., Mckinzie, D. L., et al. (2006). Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral and corticolimbic neurochemical stress responses in mice. Neuropsychopharmacology 31, 1135–1145. doi: 10.1038/sj.npp.1300913.
355. Smith, D. G., Tzavara, E. T., Shaw, J., Luecke, S., Wade, M., Davis, R., et al. (2005). Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor-deficient mice. J. Neurosci. 25, 914–922. doi: 10.1523/jneurosci.4079-04.2005.
356. Sotty, F., Soulière, F., Brun, P., Chouvet, G., Steinberg, R., Soubrié, P., et al. (1998). Differential effects of neurotensin on dopamine release in the caudal and rostral nucleus accumbens: a combined in vivo electrochemical and electrophysiological study. Neuroscience 85, 1173–1182. doi: 10.1016/s0306-4522(97)00691-x.
357. Srinivasan, S., Simms, J. A., Nielsen, C. K., Lieske, S. P., Bito-Onon, J. J., Yi, H., et al. (2012). The dual orexin/hypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self-administration. PLoS One 7:e44726. doi: 10.1371/journal.pone.0044726.
358. Stanley, B. G., Hoebel, B. G., and Leibowitz, S. F. (1983). Neurotensin: effects of hypothalamic and intravenous injections on eating and drinking in rats. Peptides 4, 493–500. doi: 10.1016/0196-9781(83)90054-2.
359. Stanley, S., Pinto, S., Segal, J., Pérez, C. A., Viale, A., Defalco, J., et al. (2010). Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc. Natl. Acad. Sci. U S A 107, 7024–7029. doi: 10.1073/pnas.100279010.
360. Steinberg, R., Brun, P., Fournier, M., Souilhac, J., Rodier, D., Mons, G., et al. (1994). SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission. Neuroscience 59, 921–929. doi: 10.1016/0306-4522(94)90295-x.
361. Stellar, E. (1954). The physiology of motivation. Psychol. Rev. 61, 5–22. doi: 10.1037/h0060347.
362. Sternson, S. M. (2013). Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77, 810–824. doi: 10.1016/j.neuron.2013.02.018.
363. Strawn, J. R., Pyne-Geithman, G. J., Ekhator, N. N., Horn, P. S., Uhde, T. W., Shutter, L. A., et al. (2010). Low cerebrospinal fluid and plasma orexin-A (hypocretin-1) concentrations in combat-related posttraumatic stress disorder. Psychoneuroendocrinology 35, 1001–1007. doi: 10.1016/j.psyneuen.2010.01.001.
364. Swanson, L. W., Sanchez-Watts, G., and Watts, A. G. (2005). Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone. Neurosci. Lett. 387, 80–84. doi: 10.1016/j.neulet.2005.06.066.
365. Swinburn, B. A., Sacks, G., Hall, K. D., Mcpherson, K., Finegood, D. T., Moodie, M. L., et al. (2011). The global obesity pandemic: shaped by global drivers and local environments. Lancet 378, 804–814. doi: 10.1016/s0140-6736(11)60813-1.
366. Szczypka, M. S., Rainey, M. A., Kim, D. S., Alaynick, W. A., Marck, B. T., Matsumoto, A. M., et al. (1999). Feeding behavior in dopamine-deficient mice. Proc. Natl. Acad. Sci. U S A 96, 12138–12143. doi: 10.1073/pnas.96.21.12138.
367. Szczypka, M. S., Rainey, M. A., and Palmiter, R. D. (2000). Dopamine is required for hyperphagia in Lep(ob/ob) mice. Nat. Genet. 25, 102–104. doi: 10.1038/75484.
368. Szigethy, E., and Beaudet, A. (1989). Correspondence between high affinity 125I-neurotensin binding sites and dopaminergic neurons in the rat substantia nigra and ventral tegmental area: a combined radioautographic and immunohistochemical light microscopic study. J. Comp. Neurol. 279, 128–137. doi: 10.1002/cne.902790111.
369. Tabuchi, S., Tsunematsu, T., Black, S. W., Tominaga, M., Maruyama, M., Takagi, K., et al. (2014). Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J. Neurosci. 34, 6495–6509. doi: 10.1523/jneurosci.0073-14.2014.
370. Taha, S. A., and Fields, H. L. (2006). Inhibitions of nucleus accumbens neurons encode a gating signal for reward-directed behavior. J. Neurosci. 26, 217–222. doi: 10.1523/jneurosci.3227-05.2006.
371. Tanaka, K., Masu, M., and Nakanishi, S. (1990). Structure and functional expression of the cloned rat neurotensin receptor. Neuron 4, 847–854. doi: 10.1016/0896-6273(90)90137-5.
372. Tang, J., Chen, J., Ramanjaneya, M., Punn, A., Conner, A. C., and Randeva, H. S. (2008). The signalling profile of recombinant human orexin-2 receptor. Cell. Signal. 20, 1651–1661. doi: 10.1016/j.cellsig.2008.05.010.
373. Teitelbaum, P. (1979). This week’s citation classic: teitalbaum P and Epstein AN. The lateral hypothalamic syndrome recovery of feeding and drinking after lateral hypothalamic lesions. Curr. Contents 11:14..
374. Teitelbaum, P., Cheng, M. F., and Rozin, P. (1969). Stages of recovery and development of lateral hypothalamic control of food and water intake. Ann. N Y Acad. Sci. 157, 849–860. doi: 10.1111/j.1749-6632.1969.tb12923.x.
375. Teitelbaum, P., and Epstein, A. N. (1962). The lateral hypothalamic syndrome: recovery of feeding and drinking after lateral hypothalamic lesions. Psychol. Rev. 69, 74–90. doi: 10.1037/h0039285.
376. Teitelbaum, P., and Stellar, E. (1954). Recovery from the failure to eat produced by hypothalamic lesions. Science 120, 894–895. doi: 10.1126/science.120.3126.894.
377. Thannickal, T. C., Lai, Y. Y., and Siegel, J. M. (2007). Hypocretin (orexin) cell loss in Parkinson’s disease. Brain 130, 1586–1595. doi: 10.1093/brain/awm097.
378. Thannickal, T. C., Moore, R. Y., Nienhuis, R., Ramanathan, L., Gulyani, S., Aldrich, M., et al. (2000). Reduced number of hypocretin neurons in human narcolepsy. Neuron 27, 469–474. doi: 10.1016/s0896-6273(00)00058-1.
379. Thorpe, A. J., and Kotz, C. M. (2005). Orexin A in the nucleus accumbens stimulates feeding and locomotor activity. Brain Res. 1050, 156–162. doi: 10.1016/j.brainres.2005.05.045.
380. Torrealba, F., Yanagisawa, M., and Saper, C. B. (2003). Colocalization of orexin a and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats. Neuroscience 119, 1033–1044. doi: 10.1016/s0306-4522(03)00238-0.
381. Toshinai, K., Date, Y., Murakami, N., Shimada, M., Mondal, M. S., Shimbara, T., et al. (2003). Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 144, 1506–1512. doi: 10.1210/en.2002-220788.
382. Toshinai, K., Yamaguchi, H., Sun, Y., Smith, R. G., Yamanaka, A., Sakurai, T., et al. (2006). Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 147, 2306–2314. doi: 10.1210/en.2005-1357.
383. Touzani, K., Tramu, G., Nahon, J. L., and Velley, L. (1993). Hypothalamic melanin-concentrating hormone and alpha-neoendorphin-immunoreactive neurons project to the medial part of the rat parabrachial area. Neuroscience 53, 865–876. doi: 10.1016/0306-4522(93)90631-o.
384. Trivedi, P., Yu, H., Macneil, D. J., Van Der Ploeg, L. H., and Guan, X. M. (1998). Distribution of orexin receptor mRNA in the rat brain. FEBS Lett. 438, 71–75. doi: 10.1016/s0014-5793(98)01266-6.
385. Tschop, M., Smiley, D. L., and Heiman, M. L. (2000). Ghrelin induces adiposity in rodents. Nature 407, 908–913. doi: 10.1038/35038090.
386. Tsunematsu, T., Kilduff, T. S., Boyden, E. S., Takahashi, S., Tominaga, M., and Yamanaka, A. (2011). Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J. Neurosci. 31, 10529–10539. doi: 10.1523/jneurosci.0784-11.2011.
387. Tsunematsu, T., Ueno, T., Tabuchi, S., Inutsuka, A., Tanaka, K. F., Hasuwa, H., et al. (2014). Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. J. Neurosci. 34, 6896–6909. doi: 10.1523/JNEUROSCI.5344-13.2014.
388. Tupone, D., Madden, C. J., Cano, G., and Morrison, S. F. (2011). An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis. J. Neurosci. 31, 15944–15955. doi: 10.1523/jneurosci.3909-11.2011.
389. Tyhon, A., Lakaye, B., Grisar, T., and Tirelli, E. (2008). Deletion of melanin-concentrating hormone receptor-1 gene accentuates D-amphetamine-induced psychomotor activation but neither the subsequent development of sensitization nor the expression of conditioned activity in mice. Pharmacol. Biochem. Behav. 88, 446–455. doi: 10.1016/j.pbb.2007.10.001.
390. Uhl, G. R. (1982). Distribution of neurotensin and its receptor in the central nervous system. Ann. N Y Acad. Sci. 400, 132–149. doi: 10.1111/j.1749-6632.1982.tb31565.x.
391. Uhl, G. R., Kuhar, M. J., and Snyder, S. H. (1977). Neurotensin: immunohistochemical localization in rat central nervous system. Proc. Natl. Acad. Sci. U S A 74, 4059–4063. doi: 10.1073/pnas.74.12.5777.
392. Uhl, G. R., and Snyder, S. H. (1977). Neurotensin receptor binding, regional and subcellular distributions favor transmitter role. Eur. J. Pharmacol. 41, 89–91. doi: 10.1016/0014-2999(77)90378-8.
393. Ungerstedt, U. (1971). Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol. Scand. Suppl. 367, 95–122. doi: 10.1111/j.1365-201x.1971.tb11001.x.
394. Vadnie, C. A., Hinton, D. J., Choi, S., Choi, Y., Ruby, C. L., Oliveros, A., et al. (2014). Activation of neurotensin receptor type 1 attenuates locomotor activity. Neuropharmacology 85C, 482–492. doi: 10.1016/j.neuropharm.2014.05.046.
395. van den Pol, A. N. (1999). Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J. Neurosci. 19, 3171–3182..
396. Vaughn, A. W., Baumeister, A. A., Hawkins, M. F., and Anticich, T. G. (1990). Intranigral microinjection of neurotensin suppresses feeding in food deprived rats. Neuropharmacology 29, 957–960. doi: 10.1016/0028-3908(90)90147-j.
397. Verret, L., Goutagny, R., Fort, P., Cagnon, L., Salvert, D., Léger, L., et al. (2003). A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep. BMC Neurosci. 4:19. doi: 10.1186/1471-2202-4-19.
398. Vincent, B., Jiracek, J., Noble, F., Loog, M., Roques, B., Dive, V., et al. (1997). Contribution of endopeptidase 3.4.24.15 to central neurotensin inactivation. Eur. J. Pharmacol. 334, 49–53. doi: 10.1016/s0014-2999(97)01209-0.
399. Vittoz, N. M., and Berridge, C. W. (2006). Hypocretin/orexin selectively increases dopamine efflux within the prefrontal cortex: involvement of the ventral tegmental area. Neuropsychopharmacology 31, 384–395. doi: 10.1038/sj.npp.1300807.
400. Vrang, N., Larsen, P. J., Clausen, J. T., and Kristensen, P. (1999). Neurochemical characterization of hypothalamic cocaine- amphetamine-regulated transcript neurons. J. Neurosci. 19:RC5..
401. Wachi, M., Okuda, M., Togashi, S., Miyashita, O., and Wakahoi, T. (1987). Effects of methamphetamine administration on brain neurotensin-like immunoreactivity in rats. Neurosci. Lett. 78, 222–226. doi: 10.1016/0304-3940(87)90637-9.
402. Walling, S. G., Nutt, D. J., Lalies, M. D., and Harley, C. W. (2004). Orexin-A infusion in the locus ceruleus triggers norepinephrine (NE) release and NE-induced long-term potentiation in the dentate gyrus. J. Neurosci. 24, 7421–7426. doi: 10.1523/jneurosci.1587-04.2004.
403. Wang, J., Osaka, T., and Inoue, S. (2001). Energy expenditure by intracerebroventricular administration of orexin to anesthetized rats. Neurosci. Lett. 315, 49–52. doi: 10.1016/s0304-3940(01)02322-9.
404. Wang, H. L., and Wu, T. (1996). G alpha q/11 mediates neurotensin excitation of substantia nigra dopaminergic neurons. Brain Res. Mol. Brain Res. 36, 29–36. doi: 10.1016/0169-328x(95)00235-k.
405. Watts, A. G. (1992). Osmotic stimulation differentially affects cellular levels of corticotropin-releasing hormone and neurotensin/neuromedin N mRNAs in the lateral hypothalamic area and central nucleus of the amygdala. Brain Res. 581, 208–216. doi: 10.1016/0006-8993(92)90710-q.
406. Watts, A. G., Kelly, A. B., and Sanchez-Watts, G. (1995). Neuropeptides and thirst: the temporal response of corticotropin-releasing hormone and neurotensin/neuromedin N gene expression in rat limbic forebrain neurons to drinking hypertonic saline. Behav. Neurosci. 109, 1146–1157. doi: 10.1037//0735-7044.109.6.1146.
407. Watts, A. G., and Sanchez-Watts, G. (2007). Rapid and preferential activation of Fos protein in hypocretin/orexin neurons following the reversal of dehydration-anorexia. J. Comp. Neurol. 502, 768–782. doi: 10.1002/cne.21316.
408. Watts, A. G., Sanchez-Watts, G., and Kelly, A. B. (1999). Distinct patterns of neuropeptide gene expression in the lateral hypothalamic area and arcuate nucleus are associated with dehydration-induced anorexia. J. Neurosci. 19, 6111–6121..
409. Werkman, T. R., Kruse, C. G., Nievelstein, H., Long, S. K., and Wadman, W. J. (2000). Neurotensin attenuates the quinpirole-induced inhibition of the firing rate of dopamine neurons in the rat substantia nigra pars compacta and the ventral tegmental area. Neuroscience 95, 417–423. doi: 10.1016/s0306-4522(99)00449-2.
410. Wienecke, M., Werth, E., Poryazova, R., Baumann-Vogel, H., Bassetti, C. L., Weller, M., et al. (2012). Progressive dopamine and hypocretin deficiencies in Parkinson’s disease: is there an impact on sleep and wakefulness? J. Sleep Res. 21, 710–717. doi: 10.1111/j.1365-2869.2012.01027.x.
411. Wilding, J. P., Gilbey, S. G., Bailey, C. J., Batt, R. A., Williams, G., Ghatei, M. A., et al. (1993). Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 132, 1939–1944. doi: 10.1210/en.132.5.1939.
412. Williams, R. H., Alexopoulos, H., Jensen, L. T., Fugger, L., and Burdakov, D. (2008). Adaptive sugar sensors in hypothalamic feeding circuits. Proc. Natl. Acad. Sci. U S A 105, 11975–11980. doi: 10.1073/pnas.0802687105.
413. Williams, G., Cardoso, H., Lee, Y. C., Ghatei, M. A., Flatt, P. R., Bailey, C. J., et al. (1991). Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. Metabolism 40, 1112–1116. doi: 10.1016/0026-0495(91)90139-n.
414. Williams, R. H., Morton, A. J., and Burdakov, D. (2011). Paradoxical function of orexin/hypocretin circuits in a mouse model of Huntington’s disease. Neurobiol. Dis. 42, 438–445. doi: 10.1016/j.nbd.2011.02.006.
415. Willie, J. T., Chemelli, R. M., Sinton, C. M., Tokita, S., Williams, S. C., Kisanuki, Y. Y., et al. (2003). Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 38, 715–730. doi: 10.1016/s0896-6273(03)00330-1.
416. Willie, J. T., Lim, M. M., Bennett, R. E., Azarion, A. A., Schwetye, K. E., and Brody, D. L. (2012). Controlled cortical impact traumatic brain injury acutely disrupts wakefulness and extracellular orexin dynamics as determined by intracerebral microdialysis in mice. J. Neurotrauma 29, 1908–1921. doi: 10.1089/neu.2012.2404.
417. Willie, J. T., Sinton, C. M., Maratos-Flier, E., and Yanagisawa, M. (2008). Abnormal response of melanin-concentrating hormone deficient mice to fasting: hyperactivity and rapid eye movement sleep suppression. Neuroscience 156, 819–829. doi: 10.1016/j.neuroscience.2008.08.048.
418. Winsky-Sommerer, R., Yamanaka, A., Diano, S., Borok, E., Roberts, A. J., Sakurai, T., et al. (2004). Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J. Neurosci. 24, 11439–11448. doi: 10.1523/jneurosci.3459-04.2004.
419. Woods, S. C., Lotter, E. C., Mckay, L. D., and Porte, D. Jr. (1979). Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282, 503–505. doi: 10.1038/282503a0.
420. Woulfe, J., and Beaudet, A. (1992). Neurotensin terminals form synapses primarily with neurons lacking detectable tyrosine hydroxylase immunoreactivity in the rat substantia nigra and ventral tegmental area. J. Comp. Neurol. 321, 163–176. doi: 10.1002/cne.903210114.
421. Wu, X., Gao, J., Yan, J., Owyang, C., and Li, Y. (2004). Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the pancreas evoked by hypoglycemia in rat. J. Neurophysiol. 91, 1734–1747. doi: 10.1152/jn.00791.2003.
422. Wu, M. F., Nienhuis, R., Maidment, N., Lam, H. A., and Siegel, J. M. (2011). Role of the hypocretin (orexin) receptor 2 (Hcrt-r2) in the regulation of hypocretin level and cataplexy. J. Neurosci. 31, 6305–6310. doi: 10.1523/jneurosci.0365-11.2011.
423. Wu, Q., Whiddon, B. B., and Palmiter, R. D. (2012). Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility. Proc. Natl. Acad. Sci. U S A 109, 3155–3160. doi: 10.1073/pnas.1120501109.
424. Xie, X., Crowder, T. L., Yamanaka, A., Morairty, S. R., Lewinter, R. D., Sakurai, T., et al. (2006). GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus. J. Physiol. 574, 399–414. doi: 10.1113/jphysiol.2006.108266.
425. Xie, X., Wisor, J. P., Hara, J., Crowder, T. L., Lewinter, R., Khroyan, T. V., et al. (2008). Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. J. Clin. Invest. 118, 2471–2481. doi: 10.1172/jci35115.
426. Yamada, M., Yamada, M., Lombet, A., Forgez, P., and Rostene, W. (1998). Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells. Life Sci. 62, 375–380. doi: 10.1016/s0024-3205(98)00192-1.
427. Yamanaka, A., Beuckmann, C. T., Willie, J. T., Hara, J., Tsujino, N., Mieda, M., et al. (2003). Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38, 701–713. doi: 10.1016/s0896-6273(03)00331-3.
428. Yamanaka, A., Sakurai, T., Katsumoto, T., Yanagisawa, M., and Goto, K. (1999). Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight. Brain Res. 849, 248–252. doi: 10.1016/s0006-8993(99)01905-8.
429. Yamanaka, A., Tabuchi, S., Tsunematsu, T., Fukazawa, Y., and Tominaga, M. (2010). Orexin directly excites orexin neurons through orexin 2 receptor. J. Neurosci. 30, 12642–12652. doi: 10.1523/JNEUROSCI.2120-10.2010.
430. Yamauchi, R., Wada, E., Kamichi, S., Yamada, D., Maeno, H., Delawary, M., et al. (2007). Neurotensin type 2 receptor is involved in fear memory in mice. J. Neurochem. 102, 1669–1676. doi: 10.1111/j.1471-4159.2007.04805.x.
431. Yoon, Y. S., and Lee, H. S. (2013). Projections from melanin-concentrating hormone (MCH) neurons to the dorsal raphe or the nuclear core of the locus coeruleus in the rat. Brain Res. 1490, 72–82. doi: 10.1016/j.brainres.2012.08.022.
432. Zahm, D. S. (1987). Neurotensin-immunoreactive neurons in the ventral striatum of the adult rat: ventromedial caudate-putamen, nucleus accumbens and olfactory tubercle. Neurosci. Lett. 81, 41–47. doi: 10.1016/0304-3940(87)90337-5.
433. Zamir, N., Skofitsch, G., Bannon, M. J., and Jacobowitz, D. M. (1986). Melanin-concentrating hormone: unique peptide neuronal system in the rat brain and pituitary gland. Proc. Natl. Acad. Sci. U S A 83, 1528–1531. doi: 10.1073/pnas.83.5.1528.
434. Zhang, J., Li, B., Yu, L., He, Y. C., Li, H. Z., Zhu, J. N., et al. (2011). A role for orexin in central vestibular motor control. Neuron 69, 793–804. doi: 10.1016/j.neuron.2011.01.026.
435. Zhang, W., Sunanaga, J., Takahashi, Y., Mori, T., Sakurai, T., Kanmura, Y., et al. (2010). Orexin neurons are indispensable for stress-induced thermogenesis in mice. J. Physiol. 588, 4117–4129. doi: 10.1113/jphysiol.2010.195099.
436. Zhang, S., Zeitzer, J. M., Sakurai, T., Nishino, S., and Mignot, E. (2007). Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy. J. Physiol. 581, 649–663. doi: 10.1113/jphysiol.2007.129510.
437. Zheng, H., Patterson, L. M., and Berthoud, H. R. (2005a). Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake and autonomic function. J. Comp. Neurol. 485, 127–142. doi: 10.1002/cne.20515.
438. Zheng, H., Patterson, L. M., Morrison, C., Banfield, B. W., Randall, J. A., Browning, K. N., et al. (2005b). Melanin concentrating hormone innervation of caudal brainstem areas involved in gastrointestinal functions and energy balance. Neuroscience 135, 611–625. doi: 10.1016/j.neuroscience.2005.06.055.
439. Zhu, Y., Miwa, Y., Yamanaka, A., Yada, T., Shibahara, M., Abe, Y., et al. (2003). Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. J. Pharmacol. Sci. 92, 259–266. doi: 10.1254/jphs.92.259.
440. Zhu, Y., Yamanaka, A., Kunii, K., Tsujino, N., Goto, K., and Sakurai, T. (2002). Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways. Physiol. Behav. 77, 251–257. doi: 10.1016/s0031-9384(02)00843-0.
441. Zigman, J. M., Nakano, Y., Coppari, R., Balthasar, N., Marcus, J. N., Lee, C. E., et al. (2005). Mice lacking ghrelin receptors resist the development of diet-induced obesity. J. Clin. Invest. 115, 3564–3572. doi: 10.1172/jci26002.