Effects of sex and deletion of neuropeptide Y2 receptors from gabaergic neurons on affective and alcohol drinking behaviors in mice

Frontiers in Integrative Neuroscience

Volumn 7, Issue 1 DEC, 2013, Pages

  McCall, Nora M ^a,e   Sprow, Gretchen M ^a,b,f   Delpire, Eric ^c,d   Thiele, Todd E ^a,b   Kash, Thomas L ^a   Pleil, Kristen E ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b University of North Carolina at Chapel Hill   (United States)

^c VANDERBILT UNIVERSITY   (United States)

^d VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF MINNESOTA   (United States)

^f DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Amygdala; Anxiety; Depression; Ethanol; Female; Gaba; NPY

Indexed keywords

ALCOHOL; NEUROPEPTIDE Y RECEPTOR AGONIST; NEUROPEPTIDE Y2 RECEPTOR;

ALCOHOL CONSUMPTION; AMYGDALOID NUCLEUS; ANHEDONIA; ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANXIETY DISORDER; ARTICLE; BRAIN REGION; CONDITIONING; CONTROLLED STUDY; DEPRESSION; DRINKING BEHAVIOR; EMOTIONALITY; FEAR; FEMALE; FORCED SWIM TEST; GABAERGIC SYSTEM; GABAERGIC TRANSMISSION; GENE DELETION; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE LOCATION; IMMUNOFLUORESCENCE TEST; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; LIGHT DARK CYCLE; LIMBIC CORTEX; MALE; MOOD DISORDER; MOUSE; NERVOUS SYSTEM ELECTROPHYSIOLOGY; NEUROFEEDBACK; NONHUMAN; OPEN FIELD TEST; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PSYCHOPHYSIOLOGY; SEX DIFFERENCE; STARTLE REFLEX; Y2R GENE;

EID: 84891553764     PISSN: 16625145     EISSN: None     Source Type: Journal    
DOI: 10.3389/fnint.2013.00100     Document Type: Article

References (83)

1. Adamec, R., Head, D., Blundell, J., Burton, P., and Berton, O. (2006). Lasting anxiogenic effects of feline predator stress in mice: sex differences in vulnerability to stress and predicting severity of anxiogenic response from the stress experience. Physiol. Behav. 88, 12-29. doi: 10.1016/j.physbeh.2006. 03.005
2. Adewale, A. S., Macarthur, H., and Westfall, T. C. (2007). Neuropeptide Y-induced enhancement of the evoked release of newly synthesized dopamine in rat striatum: mediation by Y2 receptors. Neuropharmacology 52, 1396-1402. doi: 10.1016/j.neuropharm.2007.01.018
3. Agrawal, R. G., Owen, J. A., Levin, P. S., Hewetson, A., Berman, A. E., Franklin, S. R., et al. (2013). Bioinformatics analyses reveal age-specific neuroimmune modulation as a target for treatment of high ethanol drinking. Alcohol. Clin. Exp. Res. doi: 10.1111/acer.12288 [Epub ahead of print].
4. Ammon, E., Schafer, C., Hofmann, U., and Klotz, U. (1996). Disposition and first-pass metabolism of ethanol in humans: is it gastric or hepatic and does it depend on gender? Clin. Pharmacol. Ther. 59, 503-513. doi: 10.1016/S0009-9236(96)90178-2
5. Andero, R., Brothers, S. P., Jovanovic, T., Chen, Y. T., Salah-Uddin, H., Cameron, M., et al. (2013). Amygdala-dependent fearisregulated by Oprl1 in mice and humans with PTSD. Sci. Transl. Med. 5, 188 ra173. doi: 10.1126/scitranslmed.3005656
6. Avant, L. L. (1990). Alcohol impairs visual presence/absence detection more for females than for males. Percept. Psychophys. 48, 285-290. doi: 10.3758/BF03211531
7. Bacchi, F., Mathe, A. A., Jimenez, P., Stasi, L., Arban, R., Gerrard, P., et al. (2006). Anxiolytic-like effect of the selective neuropeptide Y Y2 receptor antagonist BIIE0246 in the elevated plus-maze. Peptides 27, 3202-3207. doi: 10.1016/j.peptides.2006.07.020
8. Bannon, A. W., Seda, J., Carmouche, M., Francis, J. M., Norman, M. H., Karbon, B., et al. (2000). Behavioral characterization of neuropeptide Y knockout mice. Brain Res. 868, 79-87. doi: 10.1016/S0006-8993(00)02285-X
9. Baraona, E., Abittan, C. S., Dohmen, K., Moretti, M., Pozzato, G., Chayes, Z. W., et al. (2001). Gender differences in pharmacokinetics of alcohol. Alcohol. Clin. Exp. Res. 25, 502-507. doi: 10.1111/j.1530-0277.2001.tb02242.x
10. Becker, H. C., Anton, R. F., De Trana, C., and Randall, C. L. (1985). Sensitivity to ethanol in female mice: effects of ovariectomy and strain. Life Sci. 37, 1293-1300. doi: 10.1016/0024-3205(85)90244-9
11. Bekker, M. H., and van Mens-Verhulst, J. (2007). Anxiety disorders: sex differences in prevalence, degree, and background, but gender-neutral treatment. Gend. Med. 4, S178-S193. doi: 10.1016/S1550-8579(07)80057-X
12. Bertocchi, I., Oberto, A., Longo, A., Mele, P., Sabetta, M., Bartolomucci, A., et al. (2011). Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care. Proc. Natl. Acad. Sci. U.S.A. 108, 19395-19400. doi: 10.1073/pnas.1109468108
13. Brinks, V., de Kloet, E. R., and Oitzl, M. S. (2008). Strain specific fear behaviour and glucocorticoid response to aversive events: modelling PTSD in mice. Prog. Brain Res. 167, 257-261. doi: 10.1016/S0079-6123(07)67019-8
14. Brunssen, S. H., Moy, S. S., Toews, A. D., McPherson, C. A., and Harry, G. J. (2013). Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes. Brain Behav. Immun. 27, 42-53. doi: 10.1016/j.bbi.2012.08.017
15. Cacciaglia, R., Krause-Utz, A., Vogt, M. A., Schmahl, C., Flor, H., and Gass, P. (2013). Voluntary exercise does not ameliorate context memory and hyperarousal in a mouse model for post-traumatic stress disorder (PTSD). World J. Biol. Psychiatry 14, 403-409. doi: 10.3109/15622975.2011.583270
16. Carvajal, C., Dumont, Y., Herzog, H., and Quirion, R. (2006). Emotional behavior in aged neuropeptide Y (NPY) Y2 knockout mice. J. Mol. Neurosci. 28, 239-245. doi: 10.1385/JMN:28:3:239
17. Charney, D. S., Deutch, A. Y., Krystal, J. H., Southwick, S. M., and Davis, M. (1993). Psychobiologic mechanisms of posttraumatic stress disorder. Arch. Gen. Psychiatry 50, 295-305. doi: 10.1001/archpsyc.1993.01820160064008
18. Chee, M. J., Myers, M. G. Jr., Price, C. J., and Colmers, W. F. (2010). Neuropeptide Y suppresses anorexigenic output from the ventromedial nucleus of the hypothala-mus. J. Neurosci. 30, 3380-3390. doi: 10.1523/JNEUROSCI.4031-09.2010
19. Cryan, J. F., and Holmes, A. (2005). The ascent of mouse: advances in modelling human depression and anxiety. Nat. Rev. Drug Discov. 4, 775-790. doi: 10.1038/nrd1825
20. Dalla, C., and Shors, T. J. (2009). Sex differences in learning processes of classical and operant conditioning. Physiol. Behav. 97, 229-238. doi: 10.1016/j.physbeh.2009.02.035
21. Eckardt, M. J., Harford, T. C., Kaelber, C. T., Parker, E. S., Rosenthal, L. S., Ryback, R. S., et al. (1981). Health hazards associated with alcohol consumption. JAMA 246, 648-666. doi: 10.1001/jama.1981.03320060050022
22. Fendt, M., Burki, H., Imobersteg, S., Lingenhohl, K., McAllister, K. H., Orain, D., et al. (2009). Fear-reducing effects of intra-amygdala neuropeptide Y infusion in animal models of conditioned fear: an NPY Y1 receptor independent effect. Psychopharmacology (Berl.) 206, 291-301. doi: 10.1007/s00213-009-1610-8
23. Fraser, L. M., Brown, R. E., Hussin, A., Fontana, M., Whittaker, A., O'Leary, T. P., et al. (2010). Measuring anxiety- and locomotion-related behaviours in mice: a new way of using old tests. Psychopharmacology (Berl.) 211, 99-112. doi: 10.1007/s00213-010-1873-0
24. Frezza, M., di Padova, C., Pozzato, G., Terpin, M., Baraona, E., and Lieber, C. S. (1990). High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N. Engl. J. Med. 322, 95-99. doi: 10.1056/NEJM199001113220205
25. Frye, C. A., and Wawrzycki, J. (2003). Effect of prenatal stress and gonadal hormone condition on depressive behaviors of female and male rats. Horm. Behav. 44, 319-326. doi: 10.1016/S0018-506X(03)00159-4
26. Frye, C. A., Petralia, S. M., and Rhodes, M. E. (2000). Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3alpha, 5alpha-THP. Pharmacol. Biochem. Behav. 67, 587-596. doi: 10.1016/S0091-3057(00)00392-0
27. Gater, R., Tansella, M., Korten, A., Tiemens, B. G., Mavreas, V. G., and Olatawura, M. O. (1998). Sex differences in the prevalence and detection of depressive and anxiety disorders in general health care settings: report from the World Health Organization Collaborative Study on Psychological Problems in General Health Care. Arch. Gen. Psychiatry 55, 405-413. doi: 10.1001/archpsyc.55.5.405
28. Gilpin, N. W., Misra, K., Herman, M. A., Cruz, M. T., Koob, G. F., and Roberto, M. (2011). Neuropeptide Y opposes alcohol effects on gamma-aminobutyric acid release in amygdala and blocks the transition to alcohol dependence. Biol. Psychiatry 69, 1091-1099. doi: 10.1016/j.biopsych.2011.02.004
29. Griebel, G., and Holmes, A. (2013). 50 years of hurdles and hope in anxiolytic drug discovery. Nat. Rev. Drug Discov. 12, 667-687. doi: 10.1038/nrd4075
30. Hall, F. S., Sora, I., and Uhl, G. R. (2003). Sex-dependent modulation of ethanol consumption in vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) knockout mice. Neuropsychopharmacology 28, 620-628. doi: 10.1038/sj.npp.1300070
31. Heilig, M., Soderpalm, B., Engel, J. A., and Widerlov, E. (1989). Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology (Berl.) 98, 524-529. doi: 10.1007/BF00441953
32. Huang, A. C., Shyu, B. C., Hsiao, S., Chen, T. C., and He, A. B. (2013). Neural substrates of fear conditioning, extinction, and spontaneous recovery in passive avoidance learning: a c-fos study in rats. Behav. Brain Res. 237, 23-31. doi: 10.1016/j.bbr.2012.09.024
33. Johnston, A. L., and File, S. E. (1991). Sex differences in animal tests of anxiety. Physiol. Behav. 49, 245-250. doi: 10.1016/0031-9384(91)90039-Q
34. Kallupi, M., Vendruscolo, L. F., Carmichael, C.Y., George, O., Koob, G. F., and Gilpin, N. W. (2013). Neuropeptide Y Y R blockade in the central amygdala reduces anxiety-like behavior but not alcohol drinking in alcohol-dependent rats. Addict. Biol. doi: 10.1111/adb.12059 [Epub ahead of print].
35. Karlsson, R. M., Choe, J. S., Cameron, H. A., Thorsell, A., Crawley, J. N., Holmes, A., et al. (2008). The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice. Psychopharmacology (Berl.) 195, 547-557. doi: 10.1007/s00213-007-0945-2
36. Kash, T. L., and Winder, D. G. (2006). Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate inhibitory synaptic transmission in the bed nucleus of the stria terminalis. Neuropharmacology 51, 1013-1022. doi: 10.1016/j.neuropharm.2006.06.011
37. Kask, A., Rago, L., and Harro, J. (1998). Anxiolytic-like effect of neuropeptide Y (NPY) and NPY13-36 microinjected into vicinity of locus coeruleus in rats. Brain Res. 788, 345-348. doi: 10.1016/S0006-8993(98)00076-6
38. Kennett, G. A., Curzon, G., Hunt, A., and Patel, A. J. (1986). Immobilization decreases amino acid concentrations in plasma but maintains or increases them in brain. J. Neurochem. 46, 208-212. doi: 10.1111/j.1471-4159.1986.tb12947.x
39. Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., et al. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch. Gen. Psychiatry 51, 8-19. doi: 10.1001/archpsyc.1994.03950010008002
40. Kessler, R. C., Sonnega, A., Bromet, E., Hughes, M., and Nelson, C. B. (1995). Posttraumatic stress disorder in the National Comorbidity Survey. Arch. Gen. Psychiatry 52, 1048-1060. doi: 10.1001/archpsyc.1995.03950240066012
41. Key, J., Hodgson, S., Omar, R. Z., Jensen, T. K., Thompson, S. G., Boobis, A. R., et al. (2006). Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes Control 17, 759-770. doi: 10.1007/s10552-006-0011-0
42. Krasner, N., Davis, M., Portmann, B., and Williams, R. (1977). Changing pattern of alcoholic liver disease in Great Britain: relation to sex and signs of autoimmunity. Br. Med. J. 1, 1497-1500. doi: 10.1136/bmj.1.6075.1497
43. Ledri, M., Sorensen, A. T., Erdelyi, F., Szabo, G., and Kokaia, M. (2011). Tuning afferent synapses of hippocampal interneurons by neuropeptide Y. Hippocampus 21, 198-211. doi: 10.1002/hipo.20740
44. Leret, M. L., Molina-Holgado, F., and Gonzalez, M. I. (1994). The effect of perinatal exposure to estrogens on the sexually dimorphic response to novelty. Physiol. Behav. 55, 371-373. doi: 10.1016/0031-9384(94)90148-1
45. Lewinsohn, P. M., Rohde, P., and Seeley, J. R. (1998a). Major depressive disorder in older adolescents: prevalence, risk factors, and clinical implications. Clin. Psychol. Rev. 18, 765-794. doi: 10.1016/S0272-7358(98)00010-5
46. Lewinsohn, P. M., Gotlib, I. H., Lewinsohn, M., Seeley, J. R., and Allen, N. B. (1998b). Gender differences in anxiety disorders and anxiety symptoms in adolescents. J. Abnorm. Psychol. 107, 109-117. doi: 10.1037/0021-843X.107.1.109
47. Li, C., Pleil, K. E., Stamatakis, A. M., Busan, S., Vong, L., Lowell, B. B., et al. (2012). Presynaptic inhibition of gamma-aminobutyric acid release in the bed nucleus of the stria terminalis by kappa opioid receptor signaling. Biol. Psychiatry 71, 725-732. doi: 10.1016/j.biopsych.2011.11.015
48. Lindell, S. G., Schwandt, M. L., Sun, H., Sparenborg, J. D., Bjork, K., Kasckow, J. W., et al. (2010). Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. Arch. Gen. Psychiatry 67, 423-431. doi: 10.1001/archgenpsychiatry.2010.23
49. Lowery-Gionta, E. G., Navarro, M., Li, C., Pleil, K. E., Rinker, J. A., Cox, B. R., et al. (2012). Corticotropin releasing factor signaling in the central amygdala is recruited during binge-like ethanol consumption in C57BL/6J mice. J. Neurosci. 32, 3405-3413. doi: 10.1523/JNEUROSCI.6256-11.2012
50. Marshall, A. W., Kingstone, D., Boss, M., and Morgan, M. Y. (1983). Ethanol elimination in males and females: relationship to menstrual cycle and body composition. Hepatology 3, 701-706. doi: 10.1002/hep.1840030513
51. Medina, K. L., McQueeny, T., Nagel, B. J., Hanson, K. L., Schweinsburg, A. D., and Tapert, S. F. (2008). Prefrontal cortex volumes in adolescents with alcohol use disorders: unique gender effects. Alcohol. Clin. Exp. Res. 32, 386-394. doi: 10.1111/j.1530-0277.2007.00602.x
52. Melon, L. C., Wray, K. N., Moore, E. M., and Boehm, S. L. II (2013). Sex and age differences in heavy binge drinking and its effects on alcohol respon-sivity following abstinence. Pharmacol. Biochem. Behav. 104, 177-187. doi: 10.1016/j.pbb.2013.01.005
53. Middaugh, L. D., and Kelley, B. M. (1999). Operant ethanol reward in C57BL/6 mice: influence of gender and procedural variables. Alcohol 17, 185-194. doi: 10.1016/S0741-8329(98)00056-1
54. Middaugh, L. D., Kelley, B. M., Bandy, A. L., and McGroarty, K. K. (1999). Ethanol consumption by C57BL/6 mice: influence of gender and procedural variables. Alcohol 17, 175-183. doi: 10.1016/S0741-8329(98)00055-X
55. Mozhui, K., Karlsson, R. M., Kash, T. L., Ihne, J., Norcross, M., Patel, S., et al. (2010). Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J. Neurosci. 30, 5357-5367. doi: 10.1523/JNEUROSCI.5017-09.2010
56. Nadler, J. V., Tu, B., Timofeeva, O., Jiao, Y., and Herzog, H. (2007). Neu-ropeptide Y in the recurrent mossy fiber pathway. Peptides 28, 357-364. doi: 10.1016/j.peptides.2006.07.026
57. Ohrmann, P., Pedersen, A., Braun, M., Bauer, J., Kugel, H., Kersting, A., et al. (2010). Effect of gender on processing threat-related stimuli in patients with panic disorder: sex does matter. Depress. Anxiety 27, 1034-1043. doi: 10.1002/da.20721
58. Parker, R. M., and Herzog, H. (1999). Regional distribution of Y-receptor subtype mRNAs in rat brain. Eur. J. Neurosci. 11, 1431-1448. doi: 10.1046/j.1460-9568.1999.00553.x
59. Pleil, K. E., Lopez, A., McCall, N., Jijon, A. M., Bravo, J. P., and Kash, T. L. (2012). Chronic stress alters neuropeptide Y signaling in the bed nucleus of the stria terminalis in DBA/2J but not C57BL/6J mice. Neuropharmacology 62, 1777-1786. doi: 10.1016/j.neuropharm.2011.12.002
60. Redrobe, J. P., Dumont, Y., Herzog, H., and Quirion, R. (2003). Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: evidence from Y2 receptor knockout mice. Behav. Brain Res. 141, 251-255. doi: 10.1016/S0166-4328(02)00374-1
61. Rhodes, J. S., Ford, M. M., Yu, C. H., Brown, L. L., Finn, D. A., Garland, T. Jr., et al. (2007). Mouse inbred strain differences in ethanol drinking to intoxication. Genes Brain Behav. 6, 1-18. doi: 10.1111/j.1601-183X.2006.00210.x
62. Rodgers, R. J., and Cole, J. C. (1993). Influence of social isolation, gender, strain, and prior novelty on plus-maze behaviour in mice. Physiol. Behav. 54, 729-736. doi: 10.1016/0031-9384(93)90084-S
63. Schroeder, J. P., Olive, F., Koenig, H., and Hodge, C. W. (2003). Intra-amygdala infusion of the NPY Y1 receptor antagonist BIBP 3226 attenuates operant ethanol self-administration. Alcohol. Clin. Exp. Res. 27, 1884-1891. doi: 10.1097/01.ALC.0000098875.95923.69
64. Shoblock, J. R., Welty, N., Nepomuceno, D., Lord, B., Aluisio, L., Fraser, I., et al. (2010). In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2- pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y(2) receptor. Psychopharmacology (Berl.) 208, 265-277. doi: 10.1007/s00213-009-1726-x
65. Silva, A. P., Carvalho, A. P., Carvalho, C. M., and Malva, J. O. (2001). Modulation of intracellular calcium changes and glutamate release by neuropeptide Y1 and Y2 receptors in the rat hippocampus: differential effects in CA1, CA3 and dentate gyrus. J. Neurochem. 79, 286-296. doi: 10.1046/j.1471-4159.2001. 00560.x
66. Silva, A. P., Xapelli, S., Grouzmann, E., and Cavadas, C. (2005). The putative neuroprotective role of neuropeptide Y in the central nervous system. Curr. Drug Targets CNS Neurol. Disord. 4, 331-347. doi: 10.2174/1568007054546153
67. Sparrow, A. M., Lowery-Gionta, E. G., Pleil, K. E., Li, C., Sprow, G. M., Cox, B. R., et al. (2012). Central neuropeptide Y modulates binge-like ethanol drinking in C57BL/6J miceviaY1andY2receptors. Neuropsychopharmacology 37, 1409-1421. doi: 10.1038/npp.2011.327
68. Sparta, D. R., Sparrow, A. M., Lowery, E. G., Fee, J. R., Knapp, D. J., and Thiele, T. E. (2008). Blockade of the corticotropin releasing factor type 1 receptor attenuates elevated ethanol drinking associated with drinking in the dark procedures. Alcohol. Clin. Exp. Res. 32, 259-265. doi: 10.1111/j.1530-0277.2007. 00575.x
69. Squeglia, L. M., Sorg, S. F., Schweinsburg, A. D., Wetherill, R. R., Pulido, C., and Tapert, S. F. (2012). Binge drinking differentially affects adolescent male and female brain morphometry. Psychopharmacology (Berl.) 220, 529-539. doi: 10.1007/s00213-011-2500-4
70. Stack, A., Carrier, N., Dietz, D., Hollis, F., Sorenson, J., and Kabbaj, M. (2010). Sex differences in social interaction in rats: role of the immediate-early gene zif268. Neuropsychopharmacology 35, 570-580. doi: 10.1038/npp.2009.163
71. Stanic, D., Mulder, J., Watanabe, M., and Hokfelt, T. (2011). Characterization of NPY Y2 receptor protein expression in the mouse brain. II. Coexistence with NPY, the Y1 receptor, and other neurotransmitter-related molecules. J. Comp. Neurol. 519, 1219-1257. doi: 10.1002/cne.22608
72. Tasan, R. O., Nguyen, N. K., Weger, S., Sartori, S. B., Singewald, N., Heil-bronn, R., et al. (2010). The central and basolateral amygdala are critical sites of neuropeptide Y/Y2 receptor-mediated regulation of anxiety and depression. J. Neurosci. 30, 6282-6290. doi: 10.1523/JNEUROSCI.0430-10.2010
73. ter Horst, J. P., de Kloet, E. R., Schachinger, H., and Oitzl, M. S. (2012a). Relevance of stress and female sex hormones for emotion and cognition. Cell. Mol. Neurobiol 32, 725-735. doi: 10.1007/s10571-011-9774-2
74. ter Horst, J. P., Carobrez, A. P., van der Mark, M. H., de Kloet, E. R., and Oitzl, M. S. (2012b). Sex differences in fear memory and extinction of mice with forebrain-specific disruption of the mineralocorticoid receptor. Eur. J. Neurosci. 36, 3096-3102. doi: 10.1111/j.1460-9568.2012.08237.x
75. Thiele, T. E., Naveilhan, P., and Ernfors, P. (2004). Assessment of ethanol consumption and water drinking by NPY Y(2) receptor knockout mice. Peptides 25, 975-983. doi: 10.1016/j.peptides.2004.03.009
76. Trent, N. L., and Menard, J. L. (2013). Lateral septal infusions of the neuropep-tide Y Y2 receptor agonist, NPY(13-36) differentially affect different defensive behaviors in male, Long Evans rats. Physiol. Behav. 110-111, 20-29. doi: 10.1016/j.physbeh.2012.12.011
77. Tschenett, A., Singewald, N., Carli, M., Balducci, C., Salchner, P., Vezzani, A., et al. (2003). Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors. Eur. J. Neurosci. 18, 143-148. doi: 10.1046/j.1460-9568.2003.02725.x
78. Urbano-Marquez, A., Estruch, R., Fernandez-Sola, J., Nicolas, J. M., Pare, J. C., and Rubin, E. (1995). The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men. JAMA 274, 149-154. doi: 10.1001/jama.1995.03530020067034
79. Voikar, V., Koks, S., Vasar, E., and Rauvala, H. (2001). Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies. Physiol. Behav. 72, 271-281. doi: 10.1016/S0031-9384(00)00405-4
80. Vong, L., Ye, C., Yang, Z., Choi, B., Chua, S. Jr., and Lowell, B. B. (2011). Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142-154. doi: 10.1016/j.neuron.2011.05.028
81. Zambello, E., Zanetti, L., Hedou, G. F., Angelici, O., Arban, R., Tasan, R. O. et al. (2010). Neuropeptide Y-Y2 receptor knockout mice: influence of genetic background on anxiety-related behaviors. Neuroscience 176, 420-430. doi: 10.1016/j.neuroscience.2010.10.075
82. Zhang, H., Sakharkar, A. J., Shi, G., Ugale, R., Prakash, A., and Pandey, S. C. (2010). Neuropeptide Y signaling in the central nucleus of amygdala regulates alcohol-drinking and anxiety-like behaviors of alcohol-preferring rats. Alcohol. Clin. Exp. Res. 34, 451-461. doi: 10.1111/j.1530-0277.2009.01109.x
83. Zimmerberg, B., and Farley, M. J. (1993). Sex differences in anxiety behavior in rats: role of gonadal hormones. Physiol. Behav. 54, 1119-1124. doi: 10.1016/0031-9384(93)90335-D