The hypocretins and the reward function: What have we learned so far?

Frontiers in Behavioral Neuroscience

Volumn , Issue MAY, 2013, Pages

  Boutrel, Benjamin ^a   Steiner, Nadia ^a   Halfon, Olivier ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2 METHYL 6 BENZOXAZOLYL) 3 (1,5 NAPHTHYRIDIN 4 YL)UREA; ALMOREXANT; DOPAMINE; FILOREXANT; NEUROPEPTIDE; OREXIN; OREXIN 1 RECEPTOR; OREXIN 2 RECEPTOR; OREXIN A; OREXIN B; SUVOREXANT;

ALCOHOLISM; ARTICLE; COCAINE DEPENDENCE; DOPAMINERGIC TRANSMISSION; DRINKING BEHAVIOR; DRUG DEPENDENCE; DRUG SEEKING BEHAVIOR; EXECUTIVE FUNCTION; EXPLORATORY BEHAVIOR; FEEDING BEHAVIOR; HUMAN; INSOMNIA; METABOLIC REGULATION; MOTIVATION; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); RECEPTOR BLOCKING; REINFORCEMENT; RELAPSE; REWARD; TOBACCO DEPENDENCE; WAKEFULNESS; WITHDRAWAL SYNDROME;

EID: 85172037420     PISSN: 16625153     EISSN: None     Source Type: Journal    
DOI: 10.3389/fnbeh.2013.00059     Document Type: Article

References (101)

1. Adamantidis, A., and De Lecea, L. (2008). Physiological arousal: a role for hypothalamic systems. Cell Mol Life Sci 65, 1475-1488.
2. 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.
3. Bai, Y.J., Li, Y.H., Zheng, X.G., Han, J., Yang, X.Y., and Sui, N. (2009). Orexin A attenuates unconditioned sexual motivation in male rats. Pharmacol Biochem Behav 91, 581-589.
4. Baldo, B.A., Daniel, R.A., Berridge, C.W., and Kelley, A.E. (2003). Overlapping distributions of orexin/hypocretin-and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464, 220-237.
5. Bayerlein, K., Kraus, T., Leinonen, I., Pilniok, D., Rotter, A., Hofner, B., Schwitulla, J., Sperling, W., Kornhuber, J., and Biermann, T. (2011). Orexin A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal. Alcohol 45, 541-547.
6. Berridge, C.W., Espana, R.A., and Vittoz, N.M. (2010). Hypocretin/orexin in arousal and stress. Brain Res 1314, 91-102.
7. Borgland, S.L., Chang, S.J., Bowers, M.S., Thompson, J.L., Vittoz, N., Floresco, S.B., Chou, J., Chen, B.T., and Bonci, A. (2009). Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. JNeurosci 29, 11215-11225.
8. 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.
9. Boschen, K.E., Fadel, J.R., and Burk, J.A. (2009). Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats. Psychopharmacology (Berl) 206, 205-213.
10. Boutrel, B. (2008). A neuropeptide-centric view of psychostimulant addiction. Br J Pharmacol 154, 343-357.
11. Boutrel, B., Cannella, N., and De Lecea, L. (2010). The role of hypocretin in driving arousal and goal-oriented behaviors. Brain Res 1314, 103-111.
12. Boutrel, B., and De Lecea, L. (2008). Addiction and arousal: the hypocretin connection. Physiol Behav 93, 947-951.
13. Boutrel, B., Kenny, P.J., Specio, S.E., Martin-Fardon, R., Markou, A., Koob, G.F., and De Lecea, L. (2005). Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc Natl Acad Sci U S A 102, 19168-19173.
14. Calipari, E.S., and Espana, R.A. (2012). Hypocretin/orexin regulation of dopamine signaling: implications for reward and reinforcement mechanisms. Front Behav Neurosci 6, 54.
15. Cason, A.M., and Aston-Jones, G. (2013a). Attenuation of saccharin-seeking in rats by orexin/hypocretin receptor 1 antagonist. Psychopharmacology (Berl).
16. Cason, A.M., and Aston-Jones, G. (2013b). Role of orexin/hypocretin in conditioned sucrose-seeking in rats. Psychopharmacology (Berl) 226,155-165.
17. Chemelli, R.M., Willie, J.T., Sinton, C.M., Elmquist, J.K., Scammell, T., Lee, C., Richardson, J.A., Williams, S.C., Xiong, Y., Kisanuki, Y., Fitch, T.E., Nakazato, M., Hammer, R.E., Saper, C.B., and Yanagisawa, M. (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98, 437-451.
18. Coleman, P.J., and Renger, J.J. (2010). Orexin receptor antagonists: a review of promising compounds patented since 2006. Expert Opin Ther Pat 20, 307-324.
19. Coleman, P.J., Schreier, J.D., Cox, C.D., Breslin, M.J., Whitman, D.B., Bogusky, M.J., Mcgaughey, G.B., Bednar, R.A., Lemaire, W., Doran, S.M., Fox, S.V., Garson, S.L., Gotter, A.L., Harrell, C.M., Reiss, D.R., Cabalu, T.D., Cui, D., Prueksaritanont, T., Stevens, J., Tannenbaum, P.L., Ball, R.G., Stellabott, J., Young, S.D., Hartman, G.D., Winrow, C.J., and Renger, J.J. (2012). Discovery of [(2R,5R)-5-{[(5-fluoropyridin-2_yl)oxy]methyl}_2_methylpiperidin_1_yl][5_methyl-2-(pyrimidin-2-yl)phenyl]methanone (MK-6096): a dual orexin receptor antagonist with potent sleep-promoting properties. ChemMedChem 7, 415-424, 337.
20. D'anna, K.L., and Gammie, S.C. (2006). Hypocretin-1 dose-dependently modulates maternal behaviour in mice.] Neuroendocrinol 18, 553-566.
21. Dayas, C.V., Mcgranahan, T.M., Martin-Fardon, R., and Weiss, F. (2008). Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse. Biol Psychiatry 63, 152-157.
22. De Lecea, L., Kilduff, T.S., Peyron, C., Gao, X., Foye, P.E., Danielson, P.E., Fukuhara, C., Battenberg, E.L., Gautvik, V.T., Bartlett, F.S., 2nd, Frankel, W.N., Van Den Pol, A.N., Bloom, F.E., Gautvik, K.M., and Sutcliffe, J.G. (1998). The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci ASA 95, 322-327.
23. Di Sebastiano, A.R., and Coolen, L.M. (2012). Orexin and natural reward: feeding, maternal, and male sexual behavior. Prog Brain Res 198, 65-77.
24. Di Sebastiano, A.R., Wilson-Perez, H.E., Lehman, M.N., and Coolen, L.M. (2011). Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats. Horm Behav 59,1-8.
25. Di Sebastiano, A.R., Yong-Yow, S., Wagner, L., Lehman, M.N., and Coolen, L.M. (2010). Orexin mediates initiation of sexual behavior in sexually naive male rats, but is not critical for sexual performance. Horm Behav 58, 397-404.
26. Espana, 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.
27. Espana, 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]Neurosci 31, 336-348.
28. Georgescu, D., Zachariou, V., Barrot, M., Mieda, M., Willie, J.T., Eisch, A.J., Yanagisawa, M., Nestler, E.J., and Dileone, R.J. (2003). Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal.] Neurosci 23, 3106-3111.
29. Gotter, A.L., Webber, A.L., Coleman, P.J., Renger, J.J., and Winrow, C.J. (2012). International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin receptor function, nomenclature and pharmacology. Pharmacol Rev 64, 389-420.
30. Gozzi, A., Turrini, G., Piccoli, L., Massagrande, M., Amantini, D., Antolini, M., Martinelli, P., Cesari, N., Montanari, D., Tessari, M., Corsi, M., and Bifone, A. (2011). Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists. P'oS One 6, e16406.
31. Gulia, K.K., Mallick, H.N., and Kumar, V.M. (2003). Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats. Neuroscience 116, 921-923.
32. Hamlin, A.S., Newby, J., and Mcnally, G.P. (2007). The neural correlates and role of D1 dopamine receptors in renewal of extinguished alcohol-seeking. Neuroscience 146, 525-536.
33. Harris, G.C., and Aston-Jones, G. (2006). Arousal and reward: a dichotomy in orexin function. Trends Neurosci 29, 571-577.
34. Harris, G.C., Wimmer, M., and Aston-Jones, G. (2005). A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437, 556-559.
35. Hata, T., Chen, J., Ebihara, K., Date, Y., Ishida, Y., and Nakahara, D. (2011). Intra-ventral tegmental area or intracerebroventricular orexin-A increases the intra-cranial self-stimulation threshold via activation of the corticotropin-releasing factor system in rats. Eur] Neurosci 34, 816-826.
36. Helmuth, L. (2001). Addiction. Beyond the pleasure principle. Science 294, 983-984.
37. Herring, W.J., Snyder, E., Budd, K., Hutzelmann, J., Snavely, D., Liu, K., Lines, C., Roth, T., and Michelson, D. (2012). Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology 79, 2265-2274.
38. Hollander, J.A., Lu, Q., Cameron, M.D., Kamenecka, T.M., and Kenny, P.J. (2008). Insular hypocretin transmission regulates nicotine reward. Proc Natl Acad Sci A S A 105, 19480-19485.
39. Hollander, J.A., Pham, D., Fowler, C.D., and Kenny, P.J. (2012). Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence. Front Behav Neurosci 6, 47.
40. Huang, H., Ghosh, P., and Van Den Pol, A.N. (2006). Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal.] Neurophysiol 95,1656-1668.
41. Hutcheson, D.M., Quarta, D., Halbout, B., Rigal, A., Valerio, E., and Heidbreder, C. (2011). Orexin-1 receptor antagonist SB-334867 reduces the acquisition and expression of cocaine-conditioned reinforcement and the expression of amphetamine-conditioned reward. Behav Pharmacol 22, 173-181.
42. Jahng, J.W., Kim, J.G., Kim, H.J., Kim, B.T., Kang, D.W., and Lee, J.H. (2007). Chronic food restriction in young rats results in depression-and anxiety-like behaviors with decreased expression of serotonin reuptake transporter. Brain Res 1150, 100-107.
43. Jupp, B., Krivdic, B., Krstew, E., and Lawrence, A.J. (2011a). The orexin receptor antagonist SB-334867 dissociates the motivational properties of alcohol and sucrose in rats. Brain Res 1391, 54-59.
44. Jupp, B., Krstew, E., Dezsi, G., and Lawrence, A.J. (2011b). Discrete cue-conditioned alcohol-seeking after protracted abstinence: pattern of neural activation and involvement of orexin receptors. Br] Pharmacol 162, 880-889.
45. Kenny, P.J. (2011). Tobacco dependence, the insular cortex and the hypocretin connection. Pharmacol Biochem Behav 97, 700-707.
46. Kim, A.K., Brown, R.M., and Lawrence, A.J. (2012). The role of orexins/hypocretins in alcohol use and abuse: an appetitive-reward relationship. Front Behav Neurosci 6, 78.
47. Kunii, K., Yamanaka, A., Nambu, T., Matsuzaki, I., Goto, K., and Sakurai, T. (1999). Orexins/hypocretins regulate drinking behaviour. Brain Res 842, 256-261.
48. Lawrence, A.J., Cowen, M.S., Yang, H.J., Chen, F., and Oldfield, B. (2006). The orexin system regulates alcohol-seeking in rats. Br J Pharmacol 148, 752-759.
49. Lesage, M.G., Perry, J.L., Kotz, C.M., Shelley, D., and Corrigall, W.A. (2010). Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA. Psychopharmacology (Berl) 209, 203-212.
50. Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., De Jong, P.J., Nishino, S., and Mignot, E. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98, 365-376.
51. 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.
52. Macey, D.J., Koob, G.F., and Markou, A. (2000). CRF and urocortin decreased brain stimulation reward in the rat: reversal by a CRF receptor antagonist. Brain Res 866, 82-91.
53. Markou, A., and Koob, G.F. (1991). Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4, 17-26.
54. Martin-Fardon, R., and Boutrel, B. (2012). Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry? Front Behav Neurosci 6, 75.
55. Martin-Fardon, R., and Weiss, F. (2012). N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea (SB334867), a hypocretin receptor-1 antagonist, preferentially prevents ethanol seeking: comparison with natural reward seeking. Addict Biol.
56. Martin-Fardon, R., Zorrilla, E.P., Ciccocioppo, R., and Weiss, F. (2010). Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin. Brain Res 1314, 145-161.
57. Mignot, E. (2013). Physiology. The perfect hypnotic? Science 340, 36-38.
58. Mileykovskiy, B.Y., Kiyashchenko, L.I., and Siegel, J.M. (2005). Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46, 787-798.
59. Mokdad, A.H., Marks, J.S., Stroup, D.F., and Gerberding, J.L. (2004). Actual causes of death in the United States, 2000. JAMA 291, 1238-1245.
60. Moorman, D.E., and Aston-Jones, G. (2009). Orexin-1 receptor antagonism decreases ethanol consumption and preference selectively in high-ethanol--preferring Sprague--Dawley rats. Alcohol 43, 379-386.
61. Muschamp, J.W., Dominguez, J.M., Sato, S.M., Shen, R.Y., and Hull, E.M. (2007). A role for hypocretin (orexin) in male sexual behavior. J Neurosci 27, 2837-2845.
62. Nair, S.G., Golden, S.A., and Shaham, Y. (2008). Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high-fat food self-administration and reinstatement of food seeking in rats. Br J Pharmacol 154, 406-416.
63. Narita, M., Nagumo, Y., Hashimoto, S., Khotib, J., Miyatake, M., Sakurai, T., Yanagisawa, M., Nakamachi, T., Shioda, S., and Suzuki, T. (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.
64. Nishino, S., Ripley, B., Overeem, S., Lammers, G.J., and Mignot, E. (2000). Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355, 39-40.
65. Patyal, R., Woo, E.Y., and Borgland, S.L. (2012). Local hypocretin-1 modulates terminal dopamine concentration in the nucleus accumbens shell. Front Behav Neurosci 6, 82.
66. Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., Nevsimalova, S., Aldrich, M., Reynolds, D., Albin, R., Li, R., Hungs, M., Pedrazzoli, M., Padigaru, M., Kucherlapati, M., Fan, J., Maki, R., Lammers, G.J., Bouras, C., Kucherlapati, R., Nishino, S., and Mignot, E. (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.
67. Plaza-Zabala, A., Flores, A., Maldonado, R., and Berrendero, F. (2011). Hypocretin/Orexin Signaling in the Hypothalamic Paraventricular Nucleus is Essential for the Expression of Nicotine Withdrawal. Biol Psychiatry.
68. Plaza-Zabala, A., Flores, A., Martin-Garcia, E., Saravia, R., Maldonado, R., and Berrendero, F. (2013). A Role for Hypocretin/Orexin Receptor-1 in Cue-Induced Reinstatement of Nicotine-Seeking Behavior. Neuropsychopharmacology.
69. Plaza-Zabala, A., Martin-Garcia, E., De Lecea, L., Maldonado, R., and Berrendero, F. (2010). Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior.] Neurosci 30, 2300-2310.
70. Quarta, D., Valerio, E., Hutcheson, D.M., Hedou, G., and Heidbreder, C. (2010). The orexin-1 receptor antagonist SB-334867 reduces amphetamine-evoked dopamine outflow in the shell of the nucleus accumbens and decreases the expression of amphetamine sensitization. Neurochem Int 56, 11-15.
71. Rao, Y., Mineur, Y.S., Gan, G., Wang, A.H., Liu, Z.W., Wu, X., Suyama, S., De Lecea, L., Horvath, T.L., Picciotto, M.R., and Gao, X.B. (2013). Repeated in vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin/orexin neurons in the lateral hypothalamus in mice.] Physiol.
72. Richards, J.K., Simms, J.A., Steensland, P., Taha, S.A., Borgland, S.L., Bonci, A., and Bartlett, S.E. (2008). Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats. Psychopharmacology (Berl) 199, 109-117.
73. Rieger, M., Mayer, G., and Gauggel, S. (2003). Attention deficits in patients with narcolepsy. Sleep 26, 36-43.
74. Rotter, A., Asemann, R., Decker, A., Kornhuber, J., and Biermann, T. (2011). Orexin expression and promoter-methylation in peripheral blood of patients suffering from major depressive disorder.] Affect Disord 131, 186-192.
75. Rotter, A., Bayerlein, K., Hansbauer, M., Weiland, J., Sperling, W., Kornhuber, J., and Biermann, T. (2012). Orexin A expression and promoter methylation in patients with cannabis dependence in comparison to nicotine-dependent cigarette smokers and nonsmokers. Neuropsychobiology 66, 126-133.
76. Russell, S.H., Small, C.J., Kennedy, A.R., Stanley, S.A., Seth, A., Murphy, K.G., Taheri, S., Ghatei, M.A., and Bloom, S.R. (2001). Orexin A interactions in the hypothalamo-pituitary gonadal axis. Endocrinology 142, 5294-5302.
77. Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R.M., Tanaka, H., Williams, S.C., Richardson, J.A., Kozlowski, G.P., Wilson, S., Arch, J.R., Buckingham, R.E., Haynes, A.C., Carr, S.A., Annan, R.S., Mcnulty, D.E., Liu, W.S., Terrett, J.A., Elshourbagy, N.A., Bergsma, D.J., and Yanagisawa, M. (1998). Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573-585.
78. Scammell, T.E., and Winrow, C.J. (2011). Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol 51, 243-266.
79. Schmitt, O., Usunoff, K.G., Lazarov, N.E., Itzev, D.E., Eipert, P., Rolfs, A., and Wree, A. (2011). Orexinergic innervation of the extended amygdala and basal ganglia in the rat. Brain Struct Funct.
80. Schneider, E.R., Rada, P., Darby, R.D., Leibowitz, S.F., and Hoebel, B.G. (2007). Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin. Alcohol Clin Exp Res 31, 1858-1865.
81. Schone, C., and Burdakov, D. (2012). Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons. Front Behav Neurosci 6, 81.
82. 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.
83. Sharf, R., Sarhan, M., and Dileone, R.J. (2008). Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell. Biol Psychiatry 64, 175-183.
84. Shoblock, J.R., Welty, N., Aluisio, L., Fraser, I., Motley, S.T., Morton, K., Palmer, J., Bonaventure, P., Carruthers, N.I., Lovenberg, T.W., Boggs, J., and Galici, R. (2011). Selective blockade of the orexin-2 receptor attenuates ethanol self-administration, place preference, and reinstatement. Psychopharmacology (Berl) 215, 191-203.
85. Smith, K. (2011). Trillion-dollar brain drain. Nature 478, 15.
86. 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.
87. Smith, R.J., See, R.E., and Aston-Jones, G. (2009). Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking. Eur J Neurosci 30, 493-503.
88. Sun, H., Kennedy, W.P., Wilbraham, D., Lewis, N., Calder, N., Li, X., Ma, J., Yee, K.L., Ermlich, S., Mangin, E., Lines, C., Rosen, L., Chodakewitz, J., and Murphy, G.M. (2013). Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sleep 36, 259-267.
89. Sutcliffe, J.G., and De Lecea, L. (2002). The hypocretins: setting the arousal threshold. Nat Rev Neurosci 3, 339-349.
90. Thannickal, T.C., Moore, R.Y., Nienhuis, R., Ramanathan, L., Gulyani, S., Aldrich, M., Cornford, M., and Siegel, J.M. (2000). Reduced number of hypocretin neurons in human narcolepsy. Neuron 27, 469-474.
91. Thorpe, A.J., Cleary, J.P., Levine, A.S., and Kotz, C.M. (2005). Centrally administered orexin A increases motivation for sweet pellets in rats. Psychopharmacology (Berl) 182, 75-83.
92. Tsujino, N., and Sakurai, T. (2009). Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 61, 162-176.
93. Uslaner, J.M., Tye, S.J., Eddins, D.M., Wang, X., Fox, S.V., Savitz, A.T., Binns, J., Cannon, C.E., Garson, SI., Yao, L., Hodgson, R., Stevens, J., Bowlby, M.R., Tannenbaum, P.L., Brunner, J., Mcdonald, T.P., Gotter, A.L., Kuduk, S.D., Coleman, P.J., Winrow, C.J., and Renger, J.J. (2013). Orexin receptor antagonists differ from standard sleep drugs by promoting sleep at doses that do not disrupt cognition. Sci Transl Med 5, 179ra144.
94. Von Der Goltz, C., Koopmann, A., Dinter, C., Richter, A., Grosshans, M., Fink, T., Wiedemann, K., and Kiefer, F. (2011). Involvement of orexin in the regulation of stress, depression and reward in alcohol dependence. Horm Behav 60, 644-650.
95. Von Der Goltz, C., Koopmann, A., Dinter, C., Richter, A., Rockenbach, C., Grosshans, M., Nakovics, H., Wiedemann, K., Mann, K., Winterer, G., and Kiefer, F. (2010). Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward. Psychoneuroendocrinology 35, 570-577.
96. Voorhees, C.M., and Cunningham, C.L. (2011). Involvement of the orexin/hypocretin system in ethanol conditioned place preference. Psychopharmacology (Berl) 214, 805-818.
97. Wang, B., You, Z.B., and Wise, R.A. (2009). Reinstatement of cocaine seeking by hypocretin (orexin) in the ventral tegmental area: independence from the local corticotropin-releasing factor network. Biol Psychiatry 65, 857-862.
98. Willyard, C. (2012). New class of sleep drugs may offer a safer night's rest. Nat Med 18, 996.
99. Winrow, C.J., Tanis, K.Q., Reiss, D.R., Rigby, A.M., Uslaner, J.M., Uebele, V.N., Doran, S.M., Fox, S.V., Garson, S.L., Gotter, AL, Levine, D.M., Roecker, A.J., Coleman, P.J., Koblan, K.S., and Renger, J.J. (2010). Orexin receptor antagonism prevents transcriptional and behavioral plasticity resulting from stimulant exposure. Neuropharmacology 58,185-194.
100. Yeoh, J.W., James, M.H., Jobling, P., Bains, J.S., Graham, B.A., and Dayas, C.V. (2012). Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus.] Physiol 590, 3677-3689.
101. Zhou, L., Ghee, S.M., Chan, C., Lin, L., Cameron, M.D., Kenny, P.J., and See, R.E. (2012). Orexin-1 receptor mediation of cocaine seeking in male and female rats.] Pharmacol Exp Ther 340, 801-809.