Structure-activity relationship studies on neuroactive steroids in memory, alcohol and stress-related functions: A crucial benefit from endogenous level analysis

Psychopharmacology

Volumn 231, Issue 17, 2014, Pages 3243-3255

  Vallée, Monique ^a,b  

^a INSTITUT FRANÇOIS MAGENDIE   (France)

^b UNIVERSITÉ DE BORDEAUX   (France)

Author keywords

Mass spectrometry; Neuroactive steroids; Neurosteroids; Stress; Structure activity relationships

Indexed keywords

5ALPHA DIHYDROXYPROGESTERONE; PRASTERONE; PREGNENOLONE; PROGESTERONE; PROGESTERONE RECEPTOR; STEROID; TESTOSTERONE; UNCLASSIFIED DRUG; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; ALCOHOL; CENTRAL DEPRESSANT AGENT;

ALCOHOL CONSUMPTION; BRAIN FUNCTION; BRAIN REGION; CHEMICAL STRUCTURE; HORMONE SYNTHESIS; HUMAN; MEMORY; MENTAL STRESS; NEUROMODULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; STEROID BLOOD LEVEL; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMISTRY; DRUG EFFECTS; METABOLISM; PSYCHOLOGY;

ANIMALS; CENTRAL NERVOUS SYSTEM DEPRESSANTS; ETHANOL; HUMANS; MEMORY; NEUROTRANSMITTER AGENTS; STRESS, PSYCHOLOGICAL; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84930278648     PISSN: 00333158     EISSN: 14322072     Source Type: Journal    
DOI: 10.1007/s00213-014-3593-3     Document Type: Review

References (113)

1. Akwa Y, Ladurelle N, Covey DF, Baulieu E-E (2001) The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: distinct mechanisms? Proc Natl Acad Sci U S A 98:14033-14037
2. Alomary AA, Fitzgerald RL, Purdy RH (2001) Neurosteroid analysis. Int Rev Neurobiol 46:97-115
3. Alomary AA, Vallée M, O'Dell LE, Koob GF, Purdy RH, Fitzgerald RL (2003) Acutely administered ethanol participates in testosterone synthesis and increases testosterone in rat brain. Alcohol Clin Exp Res 27:38-43
4. Asano Y (1986) Characteristics of open field behaviour of Wistar and Sprague-Dawley rats. Exp Anim 35:505-508
5. Barbaccia ML, Roscetti G, Bolacchi F, Concas A, Mostallino MC, Purdy RH, Biggio G (1996) Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil. Pharmacol Biochem Behav 54:205-210
6. Barbaccia ML, Roscetti G, Trabucchi M, Purdy RH, Mostallino MC, Concas A, Biggio G (1997) The effects of inhibitors of GABAergic transmission and stress on brain and plasma allopregnanolone concentrations. Br J Pharmacol 120:1582-1588
7. Barbaccia ML, Serra M, Purdy RH, Biggio G (2001) Stress and neuroactive steroids. Int Rev Neurobiol 46:243-272
8. Baulieu E-E (1981) Steroid hormones in the brain: several mechanisms? In: Fuxe K, Gustafsson JA, Weterberg L (eds) Steroid Hormone Regulation of the Brain. Pergamon Press, Oxford, pp 3-14
9. Baulieu E-E (1998) Neurosteroids: a novel function of the brain. Psychoneuroendocrinology 23:963-987
10. Bernardi F, Salvestroni C, Casarosa E, Nappi RE, Lanzone A, Luisi S, Purdy RH, Petraglia F, Genazzani AR (1998) Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats. Eur J Endocrinol 138:316-321
11. Biggio G, Concas A, Follesa P, Sanna E, Serra M (2007) Stress, ethanol, and neuroactive steroids. Pharmacol Ther 116:140-171
12. Bixo M, Andersson A, Winblad B, Purdy RH, Bäckström T (1997) Progesterone, 5alphapregnane-3,20-dione and 3alpha-hydroxy-5alpha-pregnane-20-one in specific regions of the human female brain in different endocrine states. Brain Res 764:173-178
13. Bowlby MR (1993) Pregnenolone sulfate potentiation of N-methyl-d-aspartate receptor channels in hippocampal neurons. Mol Pharmacol 43:813-819
14. Brambilla F, Biggio G, Pisu MG, Bellodi L, Perna G, Bogdanovich-Djukic V, Purdy RH, Serra M (2003) Neurosteroid secretion in panic disorder. Psychiatry Res 118:107-116
15. Brot MD, Akwa Y, Purdy RH, Koob GF, Britton KT (1997) The anxiolytic-like effects of the neurosteroid allopregnanolone: interactions with GABA(A) receptors. Eur J Pharmacol 325:1-7
16. Cabib S, Puglisi-Allegra S (1996) Stress, depression and the mesolimbic dopamine system. Psychopharmacol (Berl) 128:331-342
17. Caruso D, Scurati S, Maschi O, De Angelis L, Roglio I, Giatti S, Garcia-Segura LM, Melcangi RC (2008) Evaluation of neuroactive steroid levels by liquid chromatography tandem mass spectrometry in central and peripheral nervous system: effect of diabetes. Neurochem Int 52:560-568
18. Chatman K, Hollenbeck T, Hagey L, Vallée M, Purdy R, Weiss F, Siuzdak G (1999) Nanoelectrospray mass spectrometry and precursor ion monitoring for quantitative steroid analysis and attomole sensitivity. Anal Chem 71:2358-2363
19. Christakoudi S, Cowan DA, Taylor NF (2010) Steroids excreted in urine by neonates with 21-hydroxylase deficiency: characterization, using GC-MS and GC-MS/MS, of the D-ring and side chain structure of pregnanes and pregnenes. Steroids 75:34-52
20. Christianson JP, Drugan RC, Flyer JG, Watkins LR, Maier SF (2013) Anxiogenic effects of brief swim stress are sensitive to stress history. Prog Neuropsychopharmacol Biol Psychiatry 44:17-22
21. Concas A, Mostallino MC, Porcu P, Follesa P, Barbaccia ML, Trabucchi M, Purdy RH, Grisenti P, Biggio G (1998) Role of brain allopregnanolone in the plasticity of gammaaminobutyric acid type A receptor in rat brain during pregnancy and after delivery. Proc Natl Acad Sci U S A 95:13284-13289
22. Corpéchot C, Young J, Calvel M, Wehrey C, Veltz JN, Trouyer G, Mouren M, Prasad VVK, Banner C, Sjövall S, Baulieu E-E, Robel P (1993) Neurosteroids. 3α-hydroxy-5α-pregnan-20-one and its precursors in the brain, plasma, and steroidogenic glands of male and female rats. Endocrinology 133:1003-1009
23. Covey DF, Nathan D, Kalkbrenner M, Nilsson KR, Hu Y, Zorumski CF, Evers AS (2000) Enantioselectivity of pregnanolone-induced gamma-aminobutyric acid(A) receptor modulation and anesthesia. J Pharmacol Exp Ther 293:1009-1016
24. Covey DF, Evers AS, Mennerick S, Zorumski CF, Purdy RH (2001) Recent developments in structure-activity relationships for steroid modulators of GABA(A) receptors. Brain Res Brain Res Rev 37:91-97
25. Cronholm T, Makino I, Sjövall J (1971) Transfer of hydrogen from ethanol to steroids during ethanol metabolism in the rat. In Metab. Changes Induced Alc, pp 188-198
26. Czlonkowska AI, Krzascik P, Sienkiewicz-Jarosz H, Siemiatkowski M, Szyndler J, Bidzinski A, Plaznik A (2000) The effects of neurosteroids on picrotoxin-, bicuculline- and NMDA-induced seizures, and a hypnotic effect of ethanol. Pharmacol Biochem Behav 67:345-353
27. Dong E, Matsumoto K, Uzunova V, Sugaya I, Takahata H, Nomura H, Watanabe H, Costa E, Guidotti A (2001) Brain 5α-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation. Proc Natl Acad Sci U S A 98:2849-2854
28. Fanelli F, Belluomo I, Di Lallo VD, Cuomo G, De Iasio R, Baccini M, Casadio E, Casetta B, Vicennati V, Gambineri A, Grossi G, Pasquali R, Pagotto U (2011) Serum steroid profiling by isotopic dilution-liquid chromatography-mass spectrometry: comparison with current immunoassays and reference intervals in healthy adults. Steroids 76:244-253
29. George MS, Guidotti A, Rubinow D, Pan B, Mikalauskas K, Post RM (1994) CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI. Biol Psychiatry 35:775-780
30. George O, Vallée M, Vitiello S, Le Moal M, Piazza PV, Mayo W (2010) Low brain allopregnanolone levels mediate flattened circadian activity associated with memory impairments in aged rats. Biol Psychiatry 68:956-963
31. Grant KA, Helms CM, Rogers LS, Purdy RH (2008) Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys. J Pharmacol Exp Ther 326:354-361
32. Gregus A, Wintink AJ, Davis AC, Kalynchuk LE (2005) Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behav Brain Res 156:105-114
33. Griffiths WJ, Liu S, Yang Y, Purdy RH, Sjövall J (1999) Nano-electrospray tandem mass spectrometry for the analysis of neurosteroid sulphates. Rapid Commun Mass Spectrom 13:1595-1610
34. Grippo AJ, Na ES, Johnson RF, Beltz TG, Johnson AK (2004) Sucrose ingestion elicits reduced Fos expression in the nucleus accumbens of anhedonic rats. Brain Res 1019:259-264
35. Guidotti A, Dong E, Matsumoto K, Pinna G, Rasmusson AM, Costa E (2001) The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders. Brain Res Brain Res Rev 37:110-115
36. Higashi T (2006) Trace determination of steroids causing age-related diseases using LC/MS combined with detection-oriented derivatization. Chem Pharm Bull (Tokyo) 54:1479-1485
37. Higashi T, Nagahama A, Otomi N, Shimada K (2007) Studies on neurosteroids XIX. Development and validation of liquid chromatography-tandem mass spectrometric method for determination of 5alpha-reduced pregnane-type neurosteroids in rat brain and serum. J Chromatogr B Analyt Technol Biomed Life Sci 848:188-199
38. Hsu HJ, Liang MR, Chen CT, Chung BC (2006) Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement. Nature 439:480-483
39. Irwin RP, Lin SZ, Rogawski MA, Purdy RH, Paul SM (1994) Steroid potentiation and inhibition of N-methyl-d-aspartate receptor-mediated intracellular Ca++ responses: structure activity studies. J Pharmacol Exp Ther 271:677-682
40. Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837-841
41. Keski-Rahkonen P, Huhtinen K, Poutanen M, Auriola S (2011) Fast and sensitive liquid chromatography-mass spectrometry assay for seven androgenic and progestagenic steroids in human serum. J Steroid Biochem Mol Biol 127:396-404
42. Kessler RC (1997) The effects of stressful life events on depression. Annu Rev Psychol 48:191-214
43. Khisti RT, Chopde CT, Jain SP (2000) Antidepressant-like effect of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice forced swim test. Pharmacol Biochem Behav 67:137-143
44. Koal T, Schmiederer D, Pham-Tuan H, Röhring C, Rauh M (2012) Standardized LC-MS/MS based steroid hormone profile-analysis. J Steroid Biochem Mol Biol 129:129-138
45. Krone N, Hughes BA, Lavery GG, Stewart PM, Arlt W, Shackleton CH (2010) Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS). J Steroid Biochem Mol Biol 121:496-504
46. Kushnir MM, Rockwood AL, Roberts WL, Yue B, Bergquist J, Meikle AW (2011) Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories. Clin Biochem 44:77-88
47. A receptors. Prog Neurobiol 71:67-80
48. Lambert JJ, Cooper MA, Simmons RD, Weir CJ, Belelli D (2009) Neurosteroids: endogenous allosteric modulators of GABA(A) receptors. Psychoneuroendocrinology 34:S48-S58
49. Lu SF, Mo Q, Hu S, Garippa C, Simon NG (2003) Dehydroepiandrosterone upregulates neural androgen receptor level and transcriptional activity. J Neurobiol 57:163-171
50. Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232:1004-1007
51. Marx CE, Shampine LJ, Khisti RT, Trost WT, Bradford DW, Grobin AC, Massing MW, Madison RD, Butterfield MI, Lieberman JA, Morrow AL (2006a) Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Pharmacol Biochem Behav 84:609-617
52. Marx CE, Trost WT, Shampine LJ, Stevens RD, Hulette CM, Steffens DC, Ervin JF, Butterfield MI, Blazer DG, Massing MW, Lieberman JA (2006b) The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease. Biol Psychiatry 60:1287-1294
53. Maurice T, Urani A, Phan VL, Romieu P (2001) The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities. Brain Res Brain Res Rev 37:116-132
54. Melcangi RC, Garcia-Segura LM, Mensah-Nyagan AG (2008) Neuroactive steroids: state of the art and new perspectives. Cell Mol Life Sci 65:777-797
55. Mellon SH, Griffin LD (2002) Neurosteroids: biochemistry and clinical significance. Trends Endocrinol Metab 13:35-43
56. Mensah-Nyagan AG, Do-Rego JL, Beaujean D, Luu-The V, Pelletier G, Vaudry H (1999) Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol Rev 51:63-81
57. Morrow AL, Pace JR, Purdy RH, Paul SM (1990) Characterization of steroid interactions with gamma-aminobutyric acid receptor-gated chloride ion channels: evidence for multiple steroid recognition sites. Mol Pharmacol 37:263-270
58. Murakami K, Fellous A, Baulieu EE, Robel P (2000) Pregnenolone binds to microtubule associated protein 2 and stimulates microtubule assembly. Proc Natl Acad Sci U S A 97:3579-3584
59. Neumann ID, Wegener G, Homberg JR, Cohen H, Slattery DA, Zohar J, Olivier JD, Mathe AA (2010) Animal models of depression and anxiety: what do they tell us about human condition? Prog Neuropsychopharmacol Biol Psychiatry 35:1357-1375
60. A receptor pharmacology of enantiomers of dehydroepiandrosterone sulfate, pregnenolone sulfate, and (3α,5β)-3-hydroxypregnan-20-one sulfate. J Med Chem 41:2604-2613
61. O'Dell LE, Alomary AA, Vallée M, Koob GF, Fitzgerald RL, Purdy RH (2004) Ethanol induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats. Eur J Pharmacol 484:241-247
62. O'Dell LE, Purdy RH, Covey DF, Richardson HN, Roberto M, Koob GF (2005) Epipregnanolone and a novel synthetic neuroactive steroid reduce alcohol self-administration in rats. Pharmacol Biochem Behav 81:543-550
63. Park-Chung M, Wu F-S, Purdy RH, Malayev AA, Gibb TT, Farb DH (1997) Distinct sites for inverse modulation of N-methyl-d-aspartate receptors by sulfated steroids. Mol Pharmacol 52:1113-1123
64. Park-Chung M, Malayev A, Purdy RH, Gibbs TT, Farb DH (1999) Sulfated and unsulfated steroids modulate gamma-aminobutyric acidA receptor function through distinct sites. Brain Res 830:72-87
65. Patte-Mensah C, Kibaly C, Mensah-Nyagan AG (2005) Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: a potential component of nociception. Proc Natl Acad Sci U S A 102:9044-9049
66. Paul SM, Purdy RH (1992) Neuroactive steroids. FASEB J 6:2311-2322
67. Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525-529
68. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149-167
69. Poor V, Juricskay S, Gati A, Osvath P, Tenyi T (2004) Urinary steroid metabolites and 11beta-hydroxysteroid dehydrogenase activity in patients with unipolar recurrent major depression. J Affect Disord 81:55-59
70. Porcu P, O'Buckley TK, Alward SE, Marx CE, Shampine LJ, Girdler SS, Morrow AL (2009) Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum. Steroids 74:463-473
71. Porsolt RD, Brossard G, Hautbois C, Roux S (2001) Rodent models of depression: forced swimming and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci Chapter 8: Unit 8.10A
72. Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463:3-33
73. A receptors. Neuron 4:759-765
74. Purdy RH, Moore PH Jr, Rao PN, Hagino N, Yamaguchi T, Schmidt P, Rubinow DR, Morrow AL, Paul SM (1990a) Radioimmunoassay of 3 alpha-hydroxy-5 alpha-pregnan-20-one in rat and human plasma. Steroids 55:290-296
75. Purdy RH, Morrow AL, Blinn JR, Paul SM (1990b) Synthesis, metabolism, and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes. J Med Chem 33:1572-1581
76. Purdy RH, Morrow AL, Moore PH Jr, Paul SM (1991) Stress-induced elevations of gammaaminobutyric acid type A receptor-active steroids in the rat brain. Proc Natl Acad Sci U S A 88:4553-4557
77. Purdy RH, Valenzuela CF, Janak PH, Finn DA, Biggio G, Bäckström T (2005) Neuroactive steroids and ethanol. Alcohol Clin Exp Res 29:1292-1298
78. Rao PN, Purdy RH, Moore PH Jr, Goldzieher JW (1980) Synthesis of new steroid haptens for radioimmunoassay-VI. 3-O-Carboxymethyl ether derivatives of equine estrogens. Highly specific antisera for measurement of equilin and 17 alpha-dihydroequilin in plasma. J Steroid Biochem 13:1291-1298
79. Reddy DS (2010) Neurosteroids endogenous role in the human brain and therapeutic potentials. Prog Brain Res 186:113-137
80. Romeo E, Strohle A, Spalletta G, di Michele F, Hermann B, Holsboer F, Pasini A, Rupprecht R (1998) Effects of antidepressant treatment on neuroactive steroids in major depression. Am J Psychiatry 155:910-913
81. Roth RH, Tam SY, Ida Y, Yang JX, Deutch AY (1988) Stress and the mesocorticolimbic dopamine systems. Ann N Y Acad Sci 537:138-147
82. Rupprecht R, Holsboer F (2001) Neuroactive steroids in neuropsychopharmacology. Int Rev Neurobiol 46:461-477
83. Rygula R, Abumaria N, Flugge G, Fuchs E, Ruther E, Havemann-Reinecke U (2005) Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav Brain Res 162:127-134
84. A receptor activity in rat hippocampus. J Neurosci 24:6521-6530
85. Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V (2008) Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology 33:368-377
86. Schuckit MA (1998) Alcoholism and drug dependency. In: Fauci AS, Braunwald E, Isselbacher KJ et al (eds) Harrison's principles of internal medicine, 14th edn. McGraw-Hill, New York, p 2503
87. Sedlacek M, Korinek M, Petrovic M, Cais O, Adamusova E, Chodounska H, Vyklicky L Jr (2008) Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission. Physiol Res 57:S49-S57
88. Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, Usala L, Purdy RH, Biggio G (2000) Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain. J Neurochem 75:732-740
89. Serra M, Sanna E, Mostallino MC, Biggio G (2007) Social isolation stress and neuroactive steroids. Eur Neuropsychopharmacol 17:1-11
90. Southwick SM, Vythilingam M, Charney DS (2005) The psychobiology of depression and resilience to stress: implications for prevention and treatment. Annu Rev Clin Psychol 1:255-291
91. Stanczyk FZ, Clarke NJ (2010) Advantages and challenges of mass spectrometry assays for steroid hormones. J Steroid Biochem Mol Biol 121:491-495
92. Strekalova T, Spanagel R, Bartsch D, Henn FA, Gass P (2004) Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration. Neuropsychopharmacology 29:2007-2017
93. Strohle A, Romeo E, Hermann B, Pasini A, Spalletta G, di Michele F, Holsboer F, Rupprecht R (1999) Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Biol Psychiatry 45:274-277
94. Strous RD, Maayan R, Weizman A (2006) The relevance of neurosteroids to clinical psychiatry: from the laboratory to the bedside. Eur Neuropsychopharmacol 16:155-169
95. Tannenbaum B, Tannenbaum G, Anisman H (2002) Neurochemical and behavioral alterations elicited by a chronic intermittent stressor regimen: implications for allostatic load. Brain Res 953:82-92
96. Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A (1998) Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci U S A 95:3239-3244
97. Vallée M, Mayo W, Corpéchot C, Young J, Le Moal M, Baulieu E-E, Robel P, Simon H (1997) Neurosteroids: cognitive performance in deficient aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci U S A 94:14865-14870
98. Vallée M, Rivera JD, Koob GF, Purdy RH, Fitzgerald RL (2000) Quantification of neurosteroids in rat plasma and brain following swim stress and allopregnanolone administration using negative chemical ionization gas chromatography/mass spectrometry. Anal Biochem 287:153-166
99. Vallée M, Mayo W, Koob GF, Le Moal M (2001) Neurosteroids in learning and memory processes. Int Rev Neurobiol 46:273-320
100. Vallée M, Vitiello S, Bellocchio L, Hébert-Chatelain E, Monlezun S, Martin-Garcia E, Kasanetz F, Baillie GL, Panin F, Cathala A, Roullot-Lacarrière V, Fabre S, Hurst DP, Lynch DL, Shore DM, Deroche-Gamonet V, Spampinato U, Revest JM, Maldonado R, Reggio PH, Ross RA, Marsicano G, Piazza PV (2014) Pregnenolone can protect the brain from cannabis intoxication. Science 343:94-98
101. Van Broekhoven F, Verkes RJ (2003) Neurosteroids in depression: a review. Psychopharmacol (Berl) 165:97-110
102. Venard C, Boujedaini N, Belon P, Mensah-Nyagan AG, Patte-Mensah C (2008) Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine. Neuroscience 153:154-161
103. Vollmayr B, Henn FA (2003) Stress models of depression. Clin Neurosci Res 3:245-251
104. Wang Y, Griffiths WJ (2008) Capillary liquid chromatography combined with tandem mass spectrometry for the study of neurosteroids and oxysterols in brain. Neurochem Int 52:506-521
105. Wang M, Seippel L, Purdy RH, Bäckström T (1996) Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one. J Clin Endocrinol Metab 81:1076-1082
106. Wang Y, Karu K, Griffiths W (2007) Analysis of neurosterols and neurosteroids by mass spectrometry. Biochimie 89:182-191
107. Weaver CE, Land MB, Purdy RH, Richards KG, Gibbs TT, Farb DH (2000) Geometry and charge determine pharmacological effects of steroids on N-methyl-d-aspartate receptor induced Ca(2+) accumulation and cell death. J Pharmacol Exp Ther 293:747-754
108. Weng JH, Liang MR, Chen CH, Tong SK, Huang TC, Lee SP, Chen YR, Chen CT, Chung BC (2013) Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration. Nat Chem Biol 9:636-642
109. Willner P (1984) The validity of animal models of depression. Psychopharmacology 83:1-16
110. Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134:319-329
111. Willner P, Mitchell PJ (2002) The validity of animal models of predisposition to depression. Behav Pharmacol 13:169-188
112. Willner P, Muscat R, Papp M (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16:525-534
113. Wolkowitz OM, Reus VI, Chan T, Manfredi F, Raum W, Johnson R, Canick J (1999) Antiglucocorticoid treatment of depression: double-blind ketoconazole. Biol Psychiatry 45:1070-1074