Alcohol
Volume 43, Issue 7 , Pages 521-530 , November 2009

The role of neuroactive steroids in ethanol/stress interactions: proceedings of symposium VII at the Volterra conference on alcohol and stress, May 2008

  • A. Leslie Morrow

      Affiliations

    • Department of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178, USA
    • Corresponding Author InformationCorresponding author.
  • ,
  • Giovanni Biggio

      Affiliations

    • Department of Experimental Biology and Center of Excellence for the Neurobiology of Drug Dependence, University of Cagliari, Cagliari 09042, Italy
  • ,
  • Mariangela Serra

      Affiliations

    • Department of Experimental Biology and Center of Excellence for the Neurobiology of Drug Dependence, University of Cagliari, Cagliari 09042, Italy
  • ,
  • Howard C. Becker

      Affiliations

    • Charleston Alcohol Research Center, Medical University of South Carolina & VAMC, Charleston, SC 29425, USA
  • ,
  • Marcelo F. Lopez

      Affiliations

    • Charleston Alcohol Research Center, Medical University of South Carolina & VAMC, Charleston, SC 29425, USA
  • ,
  • Patrizia Porcu

      Affiliations

    • Department of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178, USA
  • ,
  • Sarah E. Alward

      Affiliations

    • Department of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178, USA
  • ,
  • Todd K. O'Buckley

      Affiliations

    • Department of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178, USA

Received 14 December 2008 ,Revised 17 March 2009 ,Accepted 9 April 2009.

References 

  1. Adinoff B, Krebaum SR, Chandler PA, Ye W, Brown MB, Williams MJ. Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness. Alcohol. Clin. Exp. Res. 2005;29:517–527
  2. Adinoff B, Krebaum SR, Chandler PA, Ye W, Brown MB, Williams MJ. Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 2: response to ovine corticotropin-releasing factor and naloxone. Alcohol. Clin. Exp. Res. 2005;29:528–537
  3. Adinoff B, Martin PR, Bone GH, Eckardt MJ, Roehrich L, George DT, et al. Hypothalamic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence. Arch. Gen. Psychiatry. 1990;47:325–330
  4. Alele PE, Devaud LL. Sex differences in steroid modulation of ethanol withdrawal in male and female rats. J. Pharmacol. Exp. Ther. 2007;320:427–436
  5. Azzolina B, Ellsworth K, Andersson S, Geissler W, Bull HG, Harris GS. Inhibition of rat alpha-reductases by finasteride: evidence for isozyme differences in the mechanism of inhibition. J. Steroid Biochem. Mol. Biol. 1997;61:55–64
  6. Barbaccia ML, Affricano D, Trabucchi M, Purdy RH, Colombo G, Agabio R, et al. Ethanol markedly increases “GABAergic” neurosteroids in alcohol-preferring rats. Eur. J. Pharmacol. 1999;384:R1–R2
  7. Barbaccia ML, Roscetti G, Bolacchi F, Concas A, Mostallino MC, Purdy RH, et al. Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil. Pharmacol. Biochem. Behav. 1996;54:205–210
  8. Bartolomucci A, Pederzani T, Sacerdote P, Panerai AE, Parmigiani S, Palanza P. Behavioral and physiological characterization of male mice under chronic psychosocial stress. Psychoneuroendocrinology. 2004;29:899–910
  9. Becker HC, Lopez MF. Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice. Alcohol. Clin. Exp. Res. 2004;28:1829–1838
  10. Belknap JK, Belknap ND, Berg JH, Coleman R. Preabsorptive vs. postabsorptive control of ethanol intake in C57BL/6J and DBA/2J mice. Behav. Genet. 1977;7:413–425
  11. Borghese CM, Harris AR. Studies of ethanol actions on recombinant δ-containing γ-aminobutyric acid type A receptors yield contradictory results. Alcohol. 2007;41:155–162
  12. Bowen CA, Purdy RH, Grant KA. Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: effect of ethanol training dose and dosing procedure. J. Pharmacol. Exp. Ther. 1999;289:405–411
  13. Brady KT, Sonne SC. The role of stress in alcohol use, alcoholism treatment, and relapse. Alcohol Res. Health. 1999;23:263–271
  14. Buck KJ, Metten P, Belknap JK, Crabbe JC. Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J. Neurosci. 1997;17:3946–3955
  15. Cagetti E, Pinna G, Guidotti A, Baicy K, Olsen RW. Chronic intermittent ethanol (CIE) administration in rats decreases levels of neurosteroids in hippocampus, accompanied by altered behavioral responses to neurosteroids and memory function. Neuropharmacology. 2004;46:570–579
  16. Chu K, Koob GF, Cole M, Zorrilla EP, Roberts AJ. Dependence-induced increases in ethanol self-administration in mice are blocked by the CRF1 receptor antagonist antalarmin and by CRF1 receptor knockout. Pharmacol. Biochem. Behav. 2007;86:813–821
  17. Clarke TK, Treutlein J, Zimmermann US, Kiefer F, Skowronek MH, Rietschel M, et al. HPA-axis activity in alcoholism: examples for a gene-environment interaction. Addict. Biol. 2008;13:1–14
  18. Costa A, Bono G, Martignoni E, Merlo P, Sances G, Nappi G. An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics. Psychoneuroendocrinology. 1996;21:263–275
  19. Crabbe JC. Provisional mapping of quantitative trait loci for chronic ethanol withdrawal severity in BXD recombinant inbred mice. J. Pharmacol. Exp. Ther. 1998;286:263–271
  20. Crabbe JC, Young ER, Kosobud A. Genetic correlations with ethanol withdrawal severity. Pharmacol. Biochem. Behav. 1983;18(Suppl 1):541–547
  21. Cunningham CL. Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice. Psychopharmacology. 1995;120:28–41
  22. de Kloet ER, Joels M, Holsboer F. Stress and the brain: from adaptation to disease. Nat. Rev. Neurosci. 2005;6:463–475
  23. Devaud LL, Purdy RH, Finn DA, Morrow AL. Sensitization of γ-aminobutyric acidA receptors to neuroactive steroids in rats during ethanol withdrawal. J. Pharmacol. Exp. Ther. 1996;278:510–517
  24. Dhaher R, Finn D, Snelling C, Hitzemann R. Lesions of the extended amygdala in C57BL/6J mice do not block the intermittent ethanol vapor-induced increase in ethanol consumption. Alcohol. Clin. Exp. Res. 2008;32:197–208
  25. Droogleever Fortuyn HA, van Broekhoven F, Span PN, Backstrom T, Zitman FG, Verkes RJ. Effects of PhD examination stress on allopregnanolone and cortisol plasma levels and peripheral benzodiazepine receptor density. Psychoneuroendocrinology. 2004;29:1341–1344
  26. Ehrenreich H, Schuck J, Stender N, Pilz J, Gefeller O, Schilling L, et al. Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcohol. Clin. Exp. Res. 1997;21:1285–1293
  27. Essrich C, Lorez M, Benson JA, Fritschy JM, Luscher B. Postsynaptic clustering of major GABAA receptor subtypes requires the γ2 subunit and gephyrin. Nat. Neurosci. 1998;1:563–571
  28. Fahlke C, Hard E, Hansen S. Facilitation of ethanol consumption by intracerebroventricular infusions of corticosterone. Psychopharmacology. 1996;127:133–139
  29. Finn DA, Ford MM, Wiren KM, Roselli CE, Crabbe JC. The role of pregnane neurosteroids in ethanol withdrawal: behavioral genetic approaches. Pharmacol. Ther. 2004;101:91–112
  30. Finn DA, Gallaher EJ, Crabbe JC. Differential change in neuroactive steroid sensitivity during ethanol withdrawal. J. Pharmacol. Exp. Ther. 2000;292:394–405
  31. Finn DA, Phillips TJ, Okorn DM, Chester JA, Cunningham CL. Rewarding effect of the neuroactive steroid 3α-hydroxy-5α-pregnan-20-one in mice. Pharmacol. Biochem. Behav. 1997;56:261–264
  32. Finn DA, Roberts AJ, Lotrich F, Gallaher EJ. Genetic differences in behavioral sensitivity to a neuroactive steroid. J. Pharmacol. Exp. Ther. 1997;280:820–828
  33. Finn DA, Sinnott RS, Ford MM, Long SL, Tanchuck MA, Phillips TJ. Sex differences in the effect of ethanol injection and consumption on brain allopregnanolone levels in C57BL/6 mice. Neuroscience. 2004;123:813–819
  34. Finn DA, Snelling C, Fretwell AM, Tanchuck MA, Underwood L, Cole M, et al. Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist D-Phe-CRF(12-41). Alcohol. Clin. Exp. Res. 2007;31:939–949
  35. Girdler SS, Klatzkin R. Neurosteroids in the context of stress: implications for depressive disorders. Pharmacol. Ther. 2007;116:125–139
  36. Grahame NJ, Cunningham CL. Intravenous ethanol self-administration in C57BL/6J and DBA/2J mice. Alcohol. Clin. Exp. Res. 1997;21:56–62
  37. Grant KA, Helms CM, Rogers LS, Purdy RH. Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys. J. Pharmacol. Exp. Ther. 2008;326:354–361
  38. Grisel JE, Metten P, Wenger CD, Merrill CM, Crabbe JC. Mapping of quantitative trait loci underlying ethanol metabolism in BXD recombinant inbred mouse strains. Alcohol. Clin. Exp. Res. 2002;26:610–616
  39. Groenink L, Dirks A, Verdouw PM, Schipholt M, Veening JG, van der Gugten J, et al. HPA axis dysregulation in mice overexpressing corticotropin releasing hormone. Biol. Psychiatry. 2002;51:875–881
  40. Hansson AC, Rimondini R, Neznanova O, Sommer WH, Heilig M. Neuroplasticity in brain reward circuitry following a history of ethanol dependence. Eur. J. Neurosci. 2008;27:1912–1922
  41. Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 2007;30:399–406
  42. Hilakivi LA, Ota M, Lister RG. Effect of isolation on brain monoamines and the behavior of mice in tests of exploration, locomotion, anxiety and behavioral ‘despair’. Pharmacol. Biochem. Behav. 1989;33:371–374
  43. Hirani K, Khisti RT, Chopde CT. Behavioral action of ethanol in Porsolt's forced swim test: modulation by 3α-hydroxy-5α-pregnan-20-one. Neuropharmacology. 2002;43:1339–1350
  44. Hirani K, Sharma AN, Jain NS, Ugale RR, Chopde CT. Evaluation of GABAergic neuroactive steroid 3α-hydroxy-5α-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats. Psychopharmacology. 2005;180:267–278
  45. Inder WJ, Joyce PR, Ellis MJ, Evans MJ, Livesey JH, Donald RA. The effects of alcoholism on the hypothalamic-pituitary-adrenal axis: interaction with endogenous opioid peptides. Clin. Endocrinol. (Oxf). 1995;43:283–290
  46. Jackson RV, Grice JE, Hockings GI, Torpy DJ. Naloxone-induced ACTH release: mechanism of action in humans. J. Pharmacol. Exp. Ther. 1995;285:518–526
  47. Janak PH, Redfern JEM, Samson HH. The reinforcing effects of ethanol are altered by the endogenous neurosteroid, allopregnanolone. Alcohol. Clin. Exp. Res. 1998;22:1106–1112
  48. Janis GC, Devaud LL, Mitsuyama H, Morrow AL. Effects of chronic ethanol consumption and withdrawal on the neuroactive steroid 3α-hydroxy-5α-pregnan-20-one in male and female rats. Alcohol. Clin. Exp. Res. 1998;22:2055–2061
  49. Khisti RT, Boyd KN, Kumar S, Morrow AL. Systemic ethanol administration elevates deoxycorticosterone levels and chronic ethanol exposure attenuates this response. Brain Res. 2005;1049:104–111
  50. Khisti RT, Penland SN, VanDoren MJ, Grobin AC, Morrow AL. GABAergic neurosteroid modulation of ethanol actions. World J. Biol. Psychiatry. 2002;3:87–95
  51. Khisti RT, VanDoren MJ, O'Buckley TK, Morrow AL. Neuroactive steroid 3α-hydroxy-5α-pregnan-20-one modulates ethanol-induced loss of righting reflex in rats. Brain Res. 2003;980:255–265
  52. Koob GF, Le Moal M. Addiction and the brain antireward system. Annu. Rev. Psychol. 2008;59:29–53
  53. Lopez MF, Anderson RI, Becker HC. Repeated cycles of chronic intermittent ethanol exposure increase both self-administration and the reinforcing value of ethanol in C57BL/6J mice. Alcohol. Clin. Exp. Res. 2008;32:163A
  54. Lopez MF, Becker HC. Effect of pattern and number of chronic ethanol exposures on subsequent voluntary ethanol intake in C57BL/6J mice. Psychopharmacology. 2005;181:688–696
  55. Matthews DB, Morrow AL, Tokunaga S, McDaniel JR. Acute ethanol administration and acute allopregnanolone administration impair spatial memory in the Morris water task. Alcohol. Clin. Exp. Res. 2002;26:1747–1751
  56. Morrow AL, Janis GC, VanDoren MJ, Matthews DB, Samson HH, Janak PH, et al. Neurosteroids mediate pharmacological effects of ethanol: a new mechanism of ethanol action?. Alcohol. Clin. Exp. Res. 1999;23:1933–1940
  57. Morrow AL, VanDoren MJ, Fleming R, Penland S. Ethanol and neurosteroid interactions in the brain. In:  Biggio G,  Purdy RH editor. International Review of Neurobiology. San Diego, CA: Academic Press; 2001;p. 349–377
  58. Morrow AL, VanDoren MJ, Penland SN, Matthews DB. The role of GABAergic neuroactive steroids in ethanol action, tolerance and dependence. Brain Res. Brain Res. Rev. 2001;37:98–109
  59. Nemeroff CB, Vale WW. The neurobiology of depression: inroads to treatment and new drug discovery. J. Clin. Psychiatry. 2005;66(Suppl 7):5–13
  60. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34:13–25
  61. Nie H, Janak PH. Comparison of reinstatement of ethanol- and sucrose-seeking by conditioned stimuli and priming injections of allopregnanolone after extinction in rats. Psychopharmacology. 2003;168:222–228
  62. O'Dell LE, Alomary AA, Vallee M, Koob GF, Fitzgerald RL, Purdy RH. Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats. Eur. J. Pharmacol. 2004;484:241–247
  63. O'Dell LE, Purdy RH, Covey DF, Richardson HN, Roberto M, Koob GF. Epipregnanolone and a novel synthetic neuroactive steroid reduce alcohol self-administration in rats. Pharmacol. Biochem. Behav. 2005;81:543–550
  64. O'Dell LE, Roberts AJ, Smith RT, Koob GF. Enhanced alcohol self-administration after intermittent versus continuous alcohol vapor exposure. Alcohol. Clin. Exp. Res. 2004;28:1676–1682
  65. Owens MJ, Ritchie JC, Nemeroff CB. 5α-Pregnane-3α,21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam. Brain Res. 1992;573:353–355
  66. Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci. 2008;31:464–468
  67. Parker V, Morinan A. The socially-isolated rat as a model for anxiety. Neuropharmacology. 1986;25:663–664
  68. Patchev VK, Hassan AHS, Holsboer F, Almeida OFX. The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus. Neuropsychopharmacology. 1996;15:533–540
  69. Patchev VK, Shoaib M, Holsboer F, Almeida OFX. The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. Neuroscience. 1994;62:265–271
  70. Phillips TJ, Crabbe JC. Behavioral studies of genetic differences in alcohol action. In:  Crabbe JC,  Harris RA editor. The Genetic Basis of Alcohol and Drug Actions. New York: Plenum Press; 1991;p. 25–104
  71. Phillips TJ, Crabbe JC, Metten P, Belknap JK. Localization of genes affecting alcohol drinking in mice. Alcohol. Clin. Exp. Res. 1994;18:931–941
  72. Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH. Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice. Alcohol. Clin. Exp. Res. 1995;19:269–278
  73. Piazza PV, Le Moal M. Glucocorticoids as a biological substrate of reward: physiological and pathophysiological implications. Brain Res. Brain Res. Rev. 1997;25:359–372
  74. Pierucci-Lagha A, Covault J, Feinn R, Nellissery M, Hernandez-Avila C, Oncken C, et al. GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride. Neuropsychopharmacology. 2005;30:1193–1203
  75. Pohorecky LA. Interaction of ethanol and stress: research with experimental animals—an update. Alcohol Alcohol. 1990;25:263–276
  76. Pohorecky LA. Stress and alcohol interaction: an update of human research. Alcohol. Clin. Exp. Res. 1991;15:438–459
  77. Porcu P, Grant KA, Green HL, Rogers LS, Morrow AL. Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys. Psychopharmacology. 2006;186:293–301
  78. Porcu, P., Grant, K.A., Morrow, A.L. (2006b). Long-term voluntary alcohol consumption increases plasma deoxycorticosterone levels and alters hypothalamic-pituitary-adrenal axis modulation in cynomolgus monkeys. 2006 Neuroscience Meeting Planner. Atlanta, GA: Society for Neuroscience. Online Program No. 192.3.
  79. Porcu P, Rogers LSM, Morrow AL, Grant KA. Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis. Pharmacol. Biochem. Behav. 2006;84:618–627
  80. Purdy RH, Morrow AL, Moore PH, Paul SM. Stress-induced elevations of γ-aminobutyric acid type A receptor-active steroids in the rat brain. Proc. Natl. Acad. Sci. U. S. A. 1991;88:4553–4557
  81. Rimondini R, Arlinde C, Sommer W, Heilig M. Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. FASEB J. 2002;16:27–35
  82. Rivier C. Effects of alcohol on the neuroendocrine system. In:  Noronha A,  Eckardt M,  Warren K editor. Review of NIAAA's Neuroscience and Behavioral Research Portfolio. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism; 2000;p. 61–81
  83. Roberts AJ, Cole M, Koob GF. Intra-amygdala muscimol decreases operant ethanol self-administration in dependent rats. Alcohol. Clin. Exp. Res. 1996;20:1289–1298
  84. Roberts AJ, Crabbe JC, Keith LD. Genetic differences in hypothalamic-pituitary-adrenal axis responsiveness to acute ethanol and acute ethanol withdrawal. Brain Res. 1992;579:296–302
  85. Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF. Excessive ethanol drinking following a history of ethanol dependence: animal model of allostasis. Neuropsychopharmacology. 2000;22:581–594
  86. Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE. Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains. Alcohol. Clin. Exp. Res. 1995;19:367–373
  87. Sanna E, Talani G, Busonero F, Pisu MG, Purdy RH, Serra M, et al. Brain steroidogenesis mediates ethanol modulation of GABAA receptor activity in rat hippocampus. J. Neurosci. 2004;24:6521–6530
  88. Serra M, Mostallino MC, Talani G, Pisu MG, Carta M, Mura ML, et al. Social isolation-induced increase in α4 and δ subunit gene expression is associated with a greater efficacy of ethanol on steroidogenesis and GABAA receptor function. J. Neurochem. 2006;98:122–133
  89. Serra M, Pisu MG, Floris I, Cara V, Purdy RH, Biggio G. Social isolation-induced increase in the sensitivity of rats to the steroidogenic effect of ethanol. J. Neurochem. 2003;85:257–263
  90. Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, et al. Social isolation-induced decreases in both the abundance of neuroactive steroids and GABAA receptor function in rat brain. J. Neurochem. 2000;75:732–740
  91. Shelton KL, Grant KA. Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice. Alcohol. Clin. Exp. Res. 2002;26:747–757
  92. Sillaber I, Henniger MS. Stress and alcohol drinking. Ann. Med. 2004;36:596–605
  93. Sinnott RS, Mark GP, Finn DA. Reinforcing effects of the neurosteroid allopregnanolone in rats. Pharmacol. Biochem. Behav. 2002;72:923–929
  94. Sinnott RS, Phillips TJ, Finn DA. Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice. Psychopharmacology. 2002;162:438–447
  95. Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR, Barr CS, et al. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biol. Psychiatry. 2008;63:139–145
  96. Spencer RL, McEwen BS. Adaptation of the hypothalamic-pituitary-adrenal axis to chronic ethanol stress. Neuroendocrinology. 1990;52:481–489
  97. Sundstrom-Poromaa I, Smith DH, Gong QH, Sabado TN, Li X, Light A, et al. Hormonally regulated α4β2δ GABAA receptors are a target for alcohol. Nat. Neurosci. 2002;5:721–722
  98. Sur C, Farrar SJ, Kerby J, Whiting PJ, Atack JR, McKernan RM. Preferential coassembly of α4 and δ subunits of the γ-aminobutyric acidA receptor in rat thalamus. Mol. Pharmacol. 1999;56:110–115
  99. Torres JM, Ortega E. Alcohol intoxication increases allopregnanolone levels in female adolescent humans. Neuropsychopharmacology. 2003;28:1207–1209
  100. Torres JM, Ortega E. Alcohol intoxication increases allopregnanolone levels in male adolescent humans. Psychopharmacology. 2004;172:352–355
  101. VanDoren MJ, Matthews DB, Janis GC, Grobin AC, Devaud LL, Morrow AL. Neuroactive steroid 3α-hydroxy-5α-pregnan-20-one modulates electrophysiological and behavioral actions of ethanol. J. Neurosci. 2000;20:1982–1989
  102. Vengeliene V, Bilbao A, Molander A, Spanagel R. Neuropharmacology of alcohol addiction. Br. J. Pharmacol. 2008;154:299–315
  103. Voikar V, Polus A, Vasar E, Rauvala H. Long-term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences. Genes Brain Behav. 2005;4:240–252
  104. Wand G. Hypothalamic-pituitary-adrenal axis: changes and risk for alcoholism. In:  Noronha A,  Eckardt M,  Warren K editor. Review of NIAAA's Neuroscience and Behavioral Research Portfolio: NIAAA Research Monograph 34. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism; 2000;p. 397–415
  105. Wand GS, Dobs AS. Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics. J. Clin. Endocrinol. Metab. 1991;72:1290–1295
  106. Wand GS, Mangold D, El Deiry S, McCaul ME, Hoover D. Family history of alcoholism and hypothalamic opiodergic activity. Arch. Gen. Psychiatry. 1998;55:1114–1119
  107. Williams KL, Ko MC, Rice KC, Woods JH. Effect of opioid receptor antagonists on hypothalamic-pituitary-adrenal activity in rhesus monkeys. Psychoneuroendocrinology. 2003;28:513–528
  108. Wongwitdecha N, Marsden CA. Social isolation increases aggressive behaviour and alters the effects of diazepam in the rat social interaction test. Behav. Brain. Res. 1996;75:27–32

PII: S0741-8329(09)00058-5

doi: 10.1016/j.alcohol.2009.04.002

Alcohol
Volume 43, Issue 7 , Pages 521-530 , November 2009