Effects and mechanisms of 3α,5α,-THP on emotion, motivation, and reward functions involving pregnane xenobiotic receptor

Frontiers in Neuroscience

Volumn , Issue JAN, 2012, Pages

  Frye, Cheryl A ^a   Paris, J J ^a   Walf, A A ^a   Rusconi, J C ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

Author keywords

Allopregnanolone; Anxiety; Lordosis; Paced mating; Progesterone; Sex differences; Stress; Ventral tegmental area

Indexed keywords

3ALPHA,5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; AGAROSE; BETA ACTIN; DOPAMINE RECEPTOR; GESTAGEN; GLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PREGNANE X RECEPTOR; UNCLASSIFIED DRUG;

ANXIETY; BIOSYNTHESIS; BRAIN CORTEX; DEPRESSION; DIENCEPHALON; DRUG ABUSE; EMOTION; HIPPOCAMPUS; HUMAN; HYPOTHALAMUS HYPOPHYSIS SYSTEM; LORDOSIS; MATING; MESENCEPHALON; MOOD DISORDER; MOTIVATION; NEUROBIOLOGY; NONHUMAN; PROTEIN LOCALIZATION; PROTEIN METABOLISM; REVIEW; REWARD; SCHIZOPHRENIA; SEX DIFFERENCE; SIGNAL TRANSDUCTION; SOCIAL ASPECT; SOCIAL BEHAVIOR; STRESS; VENTRAL TEGMENTUM; WESTERN BLOTTING;

EID: 84861933636     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2011.00136     Document Type: Review

References (249)

1. Abel, K. M., Drake, R., and Goldstein, J. M. (2010). Sex differences in schizophrenia. Int. Rev. Psychiatry 22, 417-428.
2. Altemus, M., Redwine, L. S., Leong, Y. M., Frye, C. A., Porges, S. W., and Carter, C. S. (2001). Responses to laboratory psychosocial stress in postpartum women. Psychosom. Med. 63, 814-821.
3. Altomare, G., and Capella, G. L. (2002). Depression circumstantially related to the administration of finasteride for androgenetic alopecia. J. Derma-tol. 29, 665-669.
4. Angold, A., Costello, E. J., Erkanli, A., and Worthman, C. M. (1999). Pubertal changes in hormone levels and depression in girls. Psychol. Med. 29, 1043-1053.
5. Anker, J. J., Holtz, N. A., Zlebnik, N., and Carroll, M. E. (2009). Effects of allo-pregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats. Psychopharmacology (Berl.) 203, 63-72.
6. Anker, J. J., Zlebnik, N. E., and Carroll, M. E. (2010). Differential effects of allopregnanolone on the escalation of cocaine self-administration and sucrose intake in female rats. Psychopharmacology (Berl.) 212, 419-429.
7. Bäckström, T., Andersson, A., Andreé, L., Birzniece, V., Bixo, M., Björn, I., Haage, D., Isaksson, M., Johansson, I. M., Lindblad, C., Lundgren, P., Nyberg,S.,Odmark,I. S.,Strömberg, J., Sundström-Poromaa, I., Turkmen, S., Wahlström, G., Wang, M., Wihlbäck, A. C., Zhu, D., and Zing-mark, E. (2003). Pathogenesis in menstrual cycle-linked CNS disorders. Ann. N. Y. Acad. Sci. 1007, 42-53.
8. Bäckström, T., Sanders, D., Leask, R., Davidson, D., Warner, P., and Ban-croft,J. (1983). Mood, sexuality,hor-mones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom. Med. 45, 503-507.
9. Baghai, T. C., di Michele, F., Schüle, C., Eser, D., Zwanzger, P., Pasini, A., Romeo, E., and Rupprecht, R. (2005). Plasma concentrations of neuroactive steroids before and after electroconvulsive therapy in major depression. Neuropsychopharmacol-ogy 30, 1181-1186.
10. Barbaccia, M. L., Roscetti, G., Trabuc-chi, M., Mostallino, M. C., Con-cas, A., Purdy, R. H., and Biggio, G. (1996). Time-dependent changes in rat brain neuroactive steroid concentrations and GABAA receptor function after acute stress. Neuroen-docrinology 63, 166-172.
11. Barbaccia, M. L., Roscetti, G., Trabuc-chi, M., Purdy, R. H., Mostallino, M. C., Concas, A., and Biggio, G. (1997). The effects of inhibitors of GABAer-gic transmission and stress on brain and plasma allopregnanolone concentrations. Br. J. Pharmacol. 120, 1582-15288.
12. Barbaccia, M. L., Serra, M., Purdy, R. H., and Biggio, G. (2001). Stress and neuroactive steroids. Int. Rev. Neurobiol. 46, 243-272.
13. Bauer, B., Hartz, A. M., Fricker, G., and Miller, D. S. (2004). Preg-nane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier. Mol. Pharmacol. 66, 413-419.
14. Baulieu, E. E. (1991). Neurosteroids: a new function in the brain. Biol. Cell 71, 3-10.
15. Baulieu, E. E. (1980). Steroid hormone receptors. Expos. Annu. Biochim. Med. 34, 1-25.
16. Becker, J. B., and Cha, J. H. (1989). Estrous cycle-dependent variation in amphetamine-induced behaviors and striatal dopamine release assessed with microdialysis. Behav. Brain Res. 35, 117-125.
17. Belelli, D., and Lambert, J. J. (2005). Neurosteroids: endogenous regulators of the GABAA receptor. Nat. Rev. Neurosci. 6, 565-575.
18. Benavides, J., Quarteronet, D., Imbault, F., Malgouris, C., Uzan, A., Renault, C., Dubroeucq, M. C., Gueremy, C., and Le Fur, G. (1983). Labelling of " peripheral-type" benzodiazepine binding sites in the rat brain by using [3H]PK 11195, an isoquinoline car-boxamide derivative: kinetic studies and autoradiographic localization. J. Neurochem. 41, 1744-1750.
19. Bicikova, M., Putz, Z., Hill, M., Hampl, R., Diebbelt, L., Tallova, J., and Starka, L. (1998). Serum levels of neurosteroid allopregnanolone in patients with premenstrual syndrome and patients after thyroidec-tomy. Endocr. Regul. 32, 87-92.
20. Bitran, D., Foley, M., Audette, D., Leslie, N., and Frye, C. A. (2000). Activation of peripheral mitochondr-ial benzodiazepine receptors in the hippocampus stimulates allopreg-nanolone synthesis and produces anxiolytic-like effects in the rat. Psy-chopharmacology (Berl.) 151, 64-71.
21. Bitran, D., Hilvers, R. J., and Kellogg, C. K. (1991). Anxiolytic effects of 3α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor. Brain Res. 561, 157-161.
22. Blaustein, J. D., Tetel, M. J., Riccia-rdi, K. H., Delville, Y., and Tur-cotte, J. C. (1994). Hypothalamic ovarian steroid hormone-sensitive neurons involved in female sexual behavior. Psychoneuroendocrinology 19, 505-516.
23. Boyson, S. J., McGonigle, P., and Moli-noff, P. B. (1986). Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J. Neurosci. 6, 3177-3188.
24. Brady, K. T., and Randall, C. L. (1999). Gender differences in substance use disorders. Psychiatr. Clin. North Am. 22, 241-252.
25. Braestrup, C., and Squires, R. F. (1977). Specific benzodiazepine receptors in rat brain characterized by high-affinity [3H]diazepam binding. Proc. Natl. Acad. Sci. U.S.A. 74, 3805-3809.
26. Brambilla, F., Biggio, G., Pisu, M. G., Bellodi, L., Perna, G., Bogdanovich-Djukic, V., Purdy, R. H., and Serra, M. (2003). Neurosteroid secretion in panic disorder. Psychiatry Res. 118, 107-116.
27. Brot, M. D.,Akwa,Y., Purdy, R. H., Koob, G. F., and Britton, K. T. (1997). The anxiolytic-like effects of the neu-rosteroid allopregnanolone: interactions with GABA(A) receptors. Eur. J. Pharmacol. 325, 1-7.
28. Brown, G. W., Harris, T. O., and Hep-worth, C. (1994). Life events and endogenous depression. A puzzle reexamined. Arch. Gen. Psychiatry 51, 525-534.
29. Carpenter, M. J., Upadhyaya, H. P., LaRowe, S. D., Saladin, M. E., and Brady, K. T. (2006). Menstrual cycle phase effects on nicotine withdrawal and cigarette craving: a review. Nicotine Tob. Res. 8, 627-638.
30. Carroll, B. J., Curtis, G. C., and Mendels, J. (1976). Neuroendocrine regulation in depression. II. Discrimination of depressed from nonde-pressed patients. Arch. Gen. Psychiatry 33, 1051-1058.
31. Carroll, B. J., Greden, J. F., Feinberg, M., Lohr, N., James, N. M., Steiner, M., Haskett, R. F., Albala, A. A., DeVigne, J. P., and Tarika, J. (1981). Neuroen-docrine evaluation of depression in borderline patients. Psychiatr. Clin. North Am. 4, 89-99.
32. Chaudron, L. H., Klein, M. H., Remington, P., Palta, M., Allen, C., and Essex, M. J. (2001). Predictors, prodromes and incidence of post-partum depression. J. Psychosom. Obstet. Gynaecol. 22, 103-112.
33. Chen, M. K., and Guilarte, T. R. (2008). Translocator protein 18 kDa (TSPO): molecular sensor of brain injury, and repair. Pharmacol. Ther. 118, 1-17.
34. Cheng, Y. J., and Karavolas, H. J. (1973). Conversion of progesterone to 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one by rat medical basal hypothalami and the effects of estradiol and stage of estrous cycle on the conversion. Endocrinology 93, 1157-1162.
35. Clifford, G. M., and Farmer, R. D. (2002). Drug or symptom-induced depression in men treated with α1-blockers for benign prostatic hyper-plasia? A nested case-control study. Pharmacoepidemiol. Drug Saf. 11, 55-61.
36. Compagnone, N. A., and Mellon, S. H. (2000). Neurosteroids: biosynthesis and function of these novel neuro-modulators. Front. Neuroendocrinol. 21, 1-56.
37. Cyr, M., Ghribi, O., and Di Paolo, T. (2000). Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain. J. Neuroendocrinol. 12, 445-452.
38. De Leo, V., la Marca, A., Talluri, B., D'Antona, D., and Morgante, G. (1998). Hypothalamo-pituitary-adrenal axis and adrenal function before and after ovariectomy in premenopausal women. Eur. J. Endocrinol. 138, 430-435.
39. DeBold, J. F., and Frye, C. A. (1994). Genomic and non-genomic actions of progesterone in the control of female hamster sexual behavior. Horm. Behav. 28, 445-453.
40. Dong, E., Matsumoto, K., Uzunova, V., Sugaya, I., Takahata, H., Nomura, H., Watanabe, H., Costa, E., and Guidotti, A. (2001). Brain 5α-dihydroprogesterone and allopreg-nanolone synthesis in a mouse model of protracted social isolation. Proc. Natl. Acad. Sci. U.S.A. 98, 2849-2854.
41. Dubrovsky, B. (2006). Neurosteroids, neuroactive steroids, and symptoms of affective disorders. Pharmacol. Biochem. Behav. 84, 644-655.
42. Endicott, J., Amsterdam, J., Eriksson, E., Frank, E., Freeman, E., Hirschfeld, R., Ling, F., Parry, B., Pearlstein, T., Rosenbaum, J., Rubinow, D., Schmidt, P., Severino, S., Steiner, M., Stewart, D. E., and Thys-Jacobs, S. (1999). Is premenstrual dysphoric disorder a distinct clinical entity? J. Womens Health Gend. Based Med. 8, 663-679.
43. Epperson, C. N., Haga, K., Mason, G. F., Sellers, E., Gueorguieva, R., Zhang, W., Weiss, E., Rothman, D. L., and Krystal, J. H. (2002). Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and thosewith premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch. Gen. Psychiatry 59, 851-858.
44. Erskine, M. S., and Kornberg, E. (1992). Stress and ACTH increase circulating concentrations of 3α-androstanediol in female rats. Life Sci. 51, 2065-2071.
45. Eser, D., di Michele, F., Zwanzger, P., Pasini, A., Baghai, T. C., Schüle, C., Rupprecht, R., and Romeo, E. (2005). Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3α,5α-tetrahydrodeoxycorticosterone (3α, 5α-THDOC) in healthy volunteers. Neuropsychopharmacology 30, 192-195.
46. Fáncsik, A., Linn, D. M., and Tasker, J. G. (2000). Neurosteroid modulation of GABA IPSCs is phospho-rylation dependent. J. Neurosci. 20, 67-75.
47. Freeman, E. W., Frye, C. A., Rickels, K., Martin,P. A., and Smith, S. S. (2002). Allopregnanolone levels and symptom improvement in severe premenstrual syndrome. J. Clin. Psychophar-macol. 22, 516-520.
48. Freeman, E. W., Sammel, M. D., Rin-audo, P. J., and Sheng, L. (2004). Premenstrual syndrome as a predictor of menopausal symptoms. Obstet. Gynecol. 103, 960-966.
49. Frye, C. A. (2001a). The role of neu-rosteroids and non-genomic effects of progestins in the ventral tegmen-tal area in mediating sexual receptivity of rodents. Horm. Behav. 40, 226-233.
50. Frye, C. A. (2001b). The role of neuros-teroids and non-genomic effects of progestins and androgens in mediating sexual receptivity of rodents. Brain Res. Brain Res. Rev. 37, 201-222.
51. Frye, C. A. (2007). Progestins influence motivation, reward, conditioning, stress, and/or response to drugs of abuse. Pharmacol. Biochem. Behav. 86, 209-219.
52. Frye, C. A. (2009). Neurosteroids-From Basic Research to Clinical Perspectives, in Hormones/Behavior Relations of Clinical Importance, eds R. T. Rubin and D. W. Pfaff (San Diego: Academic Press), 395-416.
53. Frye, C. A. (2011). Novel substrates for, and sources of, progestogens for reproduction. J. Neuroendocrinol. 23, 961-973.
54. Frye, C. A., and Bayon, L. E. (1999). Mating stimuli influence endogenous variations in the neurosteroids 3α,5α-THP and 3α-Diol.J. Neuroen-docrinol. 11, 839-847.
55. Frye, C. A., Bayon, L. E., Pursnani, N. K., and Purdy, R. H. (1998). The neurosteroids, progesterone and 3α,5α-THP, enhance sexual motivation, receptivity, and proceptivity in female rats. Brain Res. 808, 72-83.
56. Frye, C. A., and DeBold, J. F. (1992). Muscimol facilitates sexual receptivity in hamsters when infused into the ventral tegmentum. Pharmacol. Biochem. Behav. 42, 879-887.
57. Frye, C. A., and Gardiner, S. G. (1996). Progestins can have a membrane-mediated action in rat midbrain for facilitation of sexual receptivity. Horm. Behav. 30, 682-691.
58. Frye, C. A., Koonce, C. J., Dacosta, D., Torgersen, J., and Walf, A. A. (2010). " Knocking down expression of preg-nane xenobiotic receptor in the mid-brain ventral tegmental area attenuates estrous cycle variations in anxiety, social, and reproductive behavior of rats," 2010 Neuroscience Meeting Planner (San Diego, CA: Society for Neuroscience).
59. Frye, C. A., and Leadbetter, E. A. (1994). 5α-reduced progesterone metabolites are essential in hamster VTA for sexual receptivity. Life Sci. 54, 653-659.
60. Frye, C. A., Marrone, J., and Walf, A. A. (2008a). Effects of manipulating progesterone and NMDA receptors in the ventral tegmental area for lordosis of hamsters and rats. Psy-chopharmacology (Berl.) 200, 71-80.
61. Frye, C. A., Paris, J. J., and Rhodes, M. E. (2008b). Exploratory, anti-anxiety, social, and sexual behaviors of rats in behavioral estrus is attenuated with inhibition of 3α,5α-THP formation in the midbrain ventral tegmen-tal area. Behav. Brain Res. 193, 269-276.
62. Frye, C. A., Mermelstein, P. G., and DeBold, J. F. (1992). Evidence for a non-genomic action of progestins on sexual receptivity in hamster ventral tegmental area but not hypothal-amus. Brain Res. 578, 87-93.
63. Frye, C. A., Mermelstein, P. G., and DeBold, J. F. (1993). Bicuculline infused into the hamster ventral tegmentum inhibits, while sodium valproate facilitates, sexual receptivity. Pharmacol. Biochem. Behav. 46, 1-8.
64. Frye, C. A., Murphy, R. E., and Platek, S. M. (2000a). Anti-sense oligonu-cleotides, for progestin receptors in the VMH and glutamic acid decarboxylase in the VTA, attenuate progesterone-induced lordosis in hamsters and rats. Behav. Brain Res. 115, 55-64.
65. Frye, C. A., Bayon, L. E., and Vongher, J. M. (2000b). Intravenous progesterone elicits a more rapid induction of lordosis in rats than does SKF38393. Psychobiology 28, 99-109.
66. Frye, C. A., and Paris, J. J. (2009). Infusions of bicuculline to the ventral tegmental area attenuates sexual, exploratory, and anti-anxiety behavior of proestrous rats. Pharmacol. Biochem. Behav. 93, 474-481.
67. Frye, C. A., and Paris, J. J. (2011a). Progesterone turnover to its 5α-reduced metabolites in the ventral tegmental area of the midbrain is essential for initiating social and affective behavior and progesterone metabolism in female rats. J. Endocrinol. Invest. 34, 188-199.
68. Frye, C. A., and Paris, J. J. (2011b). Effects of neurosteroid actions at N-methyl-d-aspartate and GABAA receptors in the midbrain ventral tegmental area for anxiety-like and mating behavior of female rats. Psychopharmacology (Berl.) 213, 93-103.
69. Frye, C. A., Paris, J. J., and Rhodes, M. E. (2007). Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5α-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex. Reproduction 133, 663-674.
70. Frye, C. A., Paris, J. J., and Rhodes, M. E. (2009). Increasing 3α,5α-THP following inhibition of neu-rosteroid biosynthesis in the ventral tegmental area reinstates anti-anxiety, social, and sexual behavior of naturally receptive rats. Reproduction 137, 119-128.
71. Frye, C. A., and Petralia, S. M. (2003a). Mitochondrial benzodiazepine receptors in the ventral tegmental area modulate sexual behaviour of cycling or hormone-primed hamsters. J. Neuroendocrinol. 15, 677-686.
72. Frye, C. A., and Petralia, S. M. (2003b). Lordosis of rats is modified by neurosteroidogenic effects of membrane benzodiazepine receptors in the ventral tegmental area. Neuroen-docrinology 77, 71-82.
73. Frye, C. A., and Rhodes, M. E. (2006a). Infusions of 5α-pregnan-3α-ol-20-one (3α,5α-THP) to the ventral tegmental area, but not the substan-tia nigra, enhance exploratory, anti-anxiety, social and sexual behaviours and concomitantly increase 3α,5α-THP concentrations in the hippocampus, diencephalon and cortex of ovariectomised oestrogen-primed rats. J. Neuroendocrinol. 18, 960-975.
74. Frye, C. A., and Rhodes, M. E. (2006b). Progestin concentrations are increased following paced mating in midbrain, hippocampus, diencephalon, and cortex of rats in behavioral estrus, but only in midbrain of diestrous rats. Neuroendocrinology 83, 336-347.
75. Frye, C. A., and Rhodes, M. E. (2007a). " The role of midbrain 3α,5α-THP in mediating exploration, anxiety, social and reproductive behavior," in Neuroactive Steroids in Brain Functions, Behavior, and Disorders: Novel Strategies for Research and Treatment, eds M. S. Ritsner and A. Weizman (Houten: Springer), 449-482.
76. Frye, C. A., and Rhodes, M. E. (2007b). " Reciprocal effects of exploration, anxiety, social, and sexual behaviors and progestins in midbrain, hippocampus, diencephalon, and cortex," in Evolutionary Molecular Strategies and Plasticity, eds M. Canonaco and R. M. Fac-ciolo (Kerala: Research Signpost), 237-260.
77. Frye, C. A., and Rhodes, M. E. (2008). Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats. Behav. Brain Res. 187, 88-99.
78. Frye, C. A., Rhodes, M. E., Petralia, S. M., Walf, A. A., Sumida, K., and Edinger, K. L. (2006a). 3α-hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors. Neuroscience 138, 1007-1014.
79. Frye, C. A., Walf, A. A., and Petralia, S. M. (2006b). Progestins' effects on sexual behaviour of female rats and hamsters involving D1 and GABA(A) receptors in the ventral tegmental area may be G-protein-dependent. Behav. Brain Res. 2172, 286-293.
80. Frye, C. A., Walf, A. A., and Petralia, S. M. (2006c). In the ventral tegmen-tal area, progestins have actions at D1 receptors for lordosis of hamsters and rats that involve GABAA receptors. Horm. Behav. 50, 332-337.
81. Frye, C. A., Walf, A. A., and Petralia, S. M. (2006d). Progestin facilitation of lordosis in rodents involves adenylyl cyclase activity in the ventral tegmental area. Horm. Behav. 50, 237-244.
82. Frye, C. A., Rhodes, M. E., Raol, Y. H., and Brooks-Kayal, A. R. (2006e). Early postnatal stimulation alters pregnane neurosteroids in the hippocampus. Psychopharmacology (Berl.) 186. 343-350.
83. Frye, C. A., and Seliga, A. M. (2003a). Effects of olanzapine infusions to the ventral tegmental area on lordosis and midbrain 3α,5α-THP concentrations in rats. Psychopharmacology (Berl.) 170, 132-139.
84. Frye, C. A., and Seliga, A. M. (2003b). Olanzapine's effects to reduce fear and anxiety and enhance social interactions coincide with increased progestin concentrations of ovariectomized rats. Psychoneu-roendocrinology 28, 657-673.
85. Frye, C. A., and Vongher, J. M. (1999). GABA(A),D1,and D5,but not prog-estin receptor, antagonist and anti-sense oligonucleotide infusions to the ventral tegmental area of cycling rats and hamsters attenuate lordosis. Behav. Brain Res. 103, 23-34.
86. Frye, C. A., and Walf, A. A. (2002). Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Horm. Behav. 41, 306-315.
87. Frye, C. A., and Walf, A. A. (2004). Hippocampal 3α,5α-THP may alter depressive behavior of pregnant and lactating rats. Pharmacol. Biochem. Behav. 78, 531-540.
88. Frye, C. A., and Walf, A. A. (2007). In the ventral tegmental area, the membrane-mediated actions of progestins for lordosis of hormone-primed hamsters involve phospho-lipase C and protein kinase C. J. Neuroendocrinol. 19, 717-724.
89. Frye, C. A., and Walf, A. A. (2008a). Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways. Steroids 73, 906-913.
90. Frye, C. A., and Walf, A. A. (2008b). In the ventral tegmental area, progesto-gens' membrane mediated actions for lordosis of rats involve the second-messenger phospholipase C. Brain Res. 1230, 218-223.
91. Frye, C. A., and Walf, A. A. (2008c). Activity of protein kinase C is important for 3α,5α-THP's actions at dopamine type 1-like and/or GABAA receptors in the ventral tegmental area for lordosis of rats. Brain Res. Bull. 77, 91-97.
92. Frye, C. A., Walf, A. A., Rhodes, M. E., and Harney, J. P. (2004a). Progesterone enhances motor, anx-iolytic, analgesic, and antidepres-sive behavior of wild-type mice, but not those deficient in type 1 5α-reductase. Brain Res. 1004, 116-124.
93. Frye, C. A., Walf, A. A., and Sumida, K. (2004b). Progestins' actions in the VTA to facilitate lordosis involve dopamine-like Type 1 and 2 receptors. Pharmacol. Biochem. Behav. 78, 405-418.
94. 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.
95. Furukawa, A., Miyatake, A., Ohnishi, T., and Ichikawa, Y. (1998). Steroidogenic acute regulatory protein (StAR) transcripts con-stitutively expressed in the adult rat central nervous system: colo-calization of StAR, cytochrome P-450SCC (CYP XIA1), and 3β-hydroxysteroid dehydrogenase in the rat brain. J. Neurochem. 71, 2231-22238.
96. Gavish, M., Bachman, I., Shoukrun, R., Katz, Y., Veenman, L., Weisinger, G., and Weizman, A. (1999). Enigma of the peripheral benzodi-azepine receptor. Pharmacol. Rev. 51, 629-650.
97. Gee, K. W., McCauley, L. D., and Lan, N. C. (1995). A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties and therapeutic potential of epalons. Crit. Rev. Neurobiol. 9, 207-227.
98. Genazzani, A. R., Petraglia, F., Bernardi, F., Casarosa, E., Salvestroni, C., Tonetti, A., Nappi, R. E., Luisi, S., Palumbo, M., Purdy, R. H., and Luisi, M. (1998). Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J. Clin. Endocrinol. Metab. 83, 2099-2103.
99. Girdler, S. S., Straneva, P. A., Light, K. C., Pedersen, C. A., and Morrow, A. L. (2001). Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric disorder. Biol. Psychiatry 49, 788-797.
100. Glick, I. D., and Bennett, S. E. (1981). Psychiatric complications of progesterone and oral contraceptives. J. Clin. Psychopharmacol. 1, 350-367.
101. Gracia, C. R., Freeman, E. W., Sammel, M. D., Lin, H., Sheng, L., and Frye, C. A. (2009). Allopregnanolone levels before and after selective serotonin reuptake inhibitor treatment of premenstrual symptoms. J. Clin. Psychopharmacol. 29, 403-405.
102. Griffin, L. D., and Mellon, S. H. (1999). Selective serotonin reup-take inhibitors directly alter activity of neurosteroidogenic enzymes. Proc. Natl. Acad. Sci. U.S.A. 96, 13512-13517.
103. Guidotti, A., and Costa, E. (1998). Can the antidysphoric and anx-iolytic profiles of selective serotonin reuptake inhibitors be related to their ability to increase brain 3α,5α-tetrahydroprogesterone (allo-pregnanolone) availability? Biol. Psychiatry 44, 865-873.
104. Guidotti, A., Dong, E., Matsumoto, K., Pinna, G., Rasmusson, A. M., and Costa, E. (2001). The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5α-dihydroprogesterone in psychiatric disorders. Brain Res. Brain Res. Rev. 37, 110-115.
105. Gulinello, M., Orman, R., and Smith, S. S. (2003). Sex differences in anxiety, sensorimotor gating and withdrawal. Eur. J. Neurosci. 17, 641-648.
106. Halbreich, U., Asnis, G. M., Shin-dledecker, R., Zumoff, B., and Nathan, R. S. (1985). Cortisol secretion in endogenous depression. II. Time-related functions. Arch. Gen. Psychiatry 42, 909-914.
107. Halbreich, U., Bancroft, J., Denner-stein, L., Endicott, J., Faccinetti, F., Genazzani, A., Morse, C., Parry, B., Rubinow, D., Reid, R., Schiff, I., and Smith, S. (1993). Men-strually Related Disorders: points of consensus, debate, and disagreement. Neuropsychopharmacology 9, 13-15.
108. Hallonquist, J. D., Seeman, M. V., Lang, M., and Rector, N. A. (1993). Variation in symptom severity over the menstrual cycle of schizophrenics. Biol. Psychiatry 33, 207-209.
109. Hammarbäck, S., Damber, J. E., and Bäckström, T. (1989). Relationship between symptom severity and hormone changes in women with premenstrual syndrome. J. Clin. Endocrinol. Metab. 68, 125-130.
110. Hammarbäck, S., Ekholm, U. B., and Bäckström, T. (1991). Spontaneous anovulation causing disappearance of cyclical symptoms in women with the premenstrual syndrome. Acta Endocrinol. 125, 132-137.
111. Harrison, N. L., and Simmonds, M. A. (1984). Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 323, 287-292.
112. Hellman, L., Yoshida, K., Zumoff, B., Levin, J., Kream, J., and Fukushima, D. K. (1976). The effect of medroxyprogesterone acetate on the pituitary-adrenal axis. J. Clin. Endocrinol. Metab. 42, 912-917.
113. Hendrick, V., Altshuler, L. L., and Burt, V. K. (1996). Course of psychiatric disorders across the menstrual cycle. Harv. Rev. Psychiatry 4, 200-207.
114. Herbison, A. E. (2001). Physiological roles for the neurosteroid allopreg-nanolone in the modulation of brain function during pregnancy and parturition. Prog. Brain Res. 133, 39-47.
115. Hirani, K., Khisti, R. T., and Chopde, C. T. (2002). Behavioral action of ethanol in Porsolt's forced swim test: modulation by 3α-hydroxy-5α-pregnan-20-one. Neuropharma-cology 43, 1339-1350.
116. Holzbauer, M. (1975). Physiological variations in the ovarian production of 5α-pregnane derivatives with sedative properties in the rat. J. Steroid Biochem. 6, 1307-1310.
117. Holzbauer, M. (1976). Proceedings: physiological aspects of the hypnotic properties of steriod hormones. Br. J. Pharmacol. 56, 382P-382P.
118. Holzbauer, M., Birmingham, M. K., De Nicola, A. F., Oliver, J. T. (1985). In vivo secretion of 3α-hydroxy-5α-pregnan-20-one, a potent anaesthetic steroid, by the adrenal gland of the rat. J. Steroid Biochem. 22, 97-102.
119. Huber, T. J., Rollnik, J., Wilhelms, J., von zur Mühlen, A., Emrich, H. M., and Schneider, U. (2001). Estradiol levels in psychotic disorders. Psychoneu-roendocrinology 26, 27-35.
120. Jacobs, A. J., Odom, M. J., Word, R. A., and Carr, B. R. (1989). Effect of oral contraceptives on adreno-corticotropin and growth hormone secretion followingCRH andGHRH administration. Contraception 40, 691-699.
121. Jain, N. S., Hirani, K., and Chopde, C. T. (2005). Reversal of caffeine-induced anxiety by neurosteroid 3-α-hydroxy-5-α-pregnane-20-one in rats. Neuropharmacology 48, 627-638.
122. Kehoe,P., Mallinson, K.,McCormick,C. M., and Frye, C. A. (2000). Central allopregnanolone is increased in rat pups in response to repeated, short episodes of neonatal isolation. Brain Res. Dev. Brain Res. 124, 133-136.
123. Kellogg, C. K., and Frye, C. A. (1999). Endogenous levels of 5α-reduced progestins and androgens in fetal vs. adult rat brains. Brain Res. Dev. Brain Res. 115, 17-24.
124. Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Esh-leman, S., Wittchen, H. U., and Kendler, K. S. (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.
125. King, S. R., Matassa, A. A., White, E. K., Walsh, L. P., Jo, Y., Rao, R. M., Stocco, D. M., and Reyland, M. E. (2004). Oxysterols regulate expression of the steroidogenic acute regulatory protein. J. Mol. Endocrinol. 32, 507-517.
126. Kohtz, A. S., Paris, J. J., and Frye, C. A. (2010). Low doses of cocaine decrease, and high doses increase, anxiety-like behavior and brain progestogen levels among intact rats. Horm. Behav. 57, 474-480.
127. Koonce, C. J., Walf, A. A., and Frye, C. A. (2012). Type 1 5α-reductase may be required for estrous cycle changes in affective behaviors of female mice. Behav. Brain. Res. 226, 376-380.
128. Korinek, M., Kapras, V., Vyklicky, V., Adamusova, E., Borovska, J., Vales, K., Stuchlik, A., Horak, M., Chodounska, H., and Vyklicky, L. Jr. (2011). Neurosteroid modulation of N-methyl-d-aspartate receptors: molecular mechanism and behavioral effects. Steroids 76, 1409-1418.
129. Kurumaji, A., Nomoto, H., Yoshikawa, T., Okubo, Y., and Toru, M. (2000). An association study between two missense variations of the ben-zodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample. J. Neural Transm. 107, 491-500.
130. Lamba, V., Yasuda, K., Lamba, J. K., Assem, M., Davila, J., Strom, S., and Schuetz, E. G. (2004). PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators. Toxicol. Appl. Pharmacol. 199, 251-265.
131. Lambert, J. J., Belelli, D., Peden, D. R., Vardy, A. W., and Peters, J. A. (2003). Neurosteroid modulation of GABAA receptors. Prog. Neurobiol. 71, 67-80.
132. Laviolette, S. R., Gallegos, R. A., Hen-riksen, S. J., and van der Kooy, D. (2004). Opiate state controls bi-directional reward signaling via GABAA receptors in the ventral tegmental area. Nat. Neurosci. 7, 160-169.
133. Laviolette, S. R., and van der Kooy, D. (2001). GABA(A) receptors in the ventral tegmental area control bidirectional reward signalling between dopaminergic and non-dopaminergic neural motivational systems. Eur. J. Neurosci. 13, 1009-1015.
134. Le Mellédo, J. M., and Baker, G. B. (2002). Neuroactive steroids and anxiety disorders. J. Psychiatry Neu-rosci. 27, 161-165.
135. Li, X., Bertics, P. J., and Karavolas, H. J. (1997). Regional distribution of cytosolic and partic-ulate 5α-dihydroprogesterone 3α-hydroxysteroid oxidoreductases in female rat brain. J. Steroid Biochem. Mol. Biol. 60, 311-318.
136. Luchetti, S., Huitinga, I., and Swaab, D. F. (2011). Neurosteroid and GABA- A receptor alterations in Alzheimer's disease, Parkinson's disease and mul tiple sclerosis. Neuroscience 191, 6-21.
137. Luisi, S., Petraglia, F., Benedetto, C., Nappi, R. E., Bernardi, F., Fadalti, M., Reis, F. M., Luisi, M., and Genazzani, A. R. (2000). Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients. J. Clin. Endocrinol. Metab. 85, 2429-2433.
138. Lukoff, D., Snyder, K., Ventura, J., and Nuechterlein, K. H. (1984). Life events, familial stress, and coping in the developmental course of schizophrenia. Schizophr. Bull. 10, 258-292.
139. MacLusky, N. J., and McEwen, B. S. (1980). Progestin receptors in rat brain: distribution and properties of cytoplasmic progestin-binding sites. Endocrinology 106, 192-202.
140. Majewska, M. D. (1992). Neuros-teroids:endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog. Neurobiol. 38, 379-395.
141. Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., and Paul, S. M. (1986). Steroid hormone metabolites are barbituratelike modulators of the GABA receptor. Science 232, 1004-1007.
142. Malla, A. K., Cortese, L., Shaw, T. S., and Ginsberg, B. (1990). Life events and relapse in schizophrenia. A one year prospective study. Soc. Psychiatry Psychiatr. Epidemiol. 25, 221-224.
143. Mani, S. (2003). Signalling mechanisms in progesterone-neurotransmitter interactions. J. Mol. Endocrinol. 30, 127-137.
144. Marini, S., Nannelli, A., Sodini, D., Dragoni, S., Valoti, M., Longo, V., and Gervasi, P. G. (2007). Expression, microsomal and mitochondr-ial activities of cytochrome P450 enzymes in brain regions from control and phenobarbital-treated rabbits. Life Sci. 80, 910-917.
145. Markou, A., Duka, T., and Prelevic, G. M. (2005). Estrogens and brain function. Hormones 4, 9-17.
146. Martínez, I., and Paredes, R. G. (2001). Only self-paced mating is rewarding in rats of both sexes. Horm. Behav. 40, 510-517.
147. Martín-García, E., and Pallarès, M. (2005). Intrahippocampal nicotine and neurosteroids effects on the anxiety-like behaviour in voluntary and chronic alcohol-drinking rats. Behav. Brain Res. 164, 117-127.
148. Marx, C. E., Duncan, G. E., Gilmore, J. H., Lieberman, J. A., and Morrow, A. L. (2000). Olanzapine increases allo-pregnanolone in the rat cerebral cortex. Biol. Psychiatry 47, 1000-1004.
149. Marx, C. E., VanDoren, M. J., Duncan, G. E., Lieberman, J. A., and Morrow, A. L. (2003). Olanzapine and cloza-pine increase the GABAergic neu-roactive steroid allopregnanolone in rodents. Neuropsychopharmacology 28, 1-13.
150. McCormick, C. M., Kehoe, P., Mallinson, K., Cecchi, L., and Frye, C. A. (2002). Neonatal isolation alters stress hormone and mesolimbic dopamine release in juvenile rats. Pharmacol. Biochem. Behav. 73, 77-85.
151. Mellon, S. H. (1994). Neurosteroids: biochemistry, modes of action, and clinical relevance. J. Clin. Endocrinol. Metab. 78, 1003-1008.
152. Mellon, S. H., and Deschepper, C. F. (1993). Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain. Brain Res. 629, 283-292.
153. Mellon, S. H., Gong, W., and Schone-mann, M. D. (2008). Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease. Brain Res. Rev. 57, 410-420.
154. Micevych, P., Soma, K. K., and Sinchak, K. (2008). Neuroprogesterone: key to estrogen positive feedback? Brain Res. Rev. 57, 470-480.
155. Micevych, P. E., and Dewing, P. (2011). Membrane-initiated estradiol signaling regulating sexual receptivity. Front. Endocrinol. (Lausanne) 2:26. doi:10.3389/fendo.2011.00026
156. Miczek, K. A., Fish, E. W., and DeBold, J. F. (2003). Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm. Behav. 44, 242-257.
157. Monteleone, P., Luisi, S., Tonetti, A., Bernardi, F., Genazzani, A. D., Luisi, M., Petraglia, F., and Genazzani, A. R. (2000). Allopregnanolone concentrations and premenstrual syndrome. Eur. J. Endocrinol. 142, 269-273.
158. Morrow, A. L., Suzdak, P. D., and Paul, S. M. (1987). Steroid hormone metabolites potentiate GABA receptor-mediated chloride ion flux with nanomolar potency. Eur. J. Pharmacol. 142, 483-485.
159. Myin-Germeys, I., Nicolson, N. A., and Delespaul, P. A. (2001). The context of delusional experiences in the daily life of patients with schizophrenia. Psychol. Med. 31, 489-498.
160. Nemeroff, C. B., Owens, M. J., Bis-sette, G., Andorn, A. C., and Stanley, M. (1988). Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch. Gen. Psychiatry 45, 577-579.
161. Norman, R. M., and Malla, A. K. (1993). Stressful life events and schizophrenia. I: a review of the research. Br. J. Psychiatry 162, 161-166.
162. Nyberg, S., Wahlström, G., Bäck-ström, T., and Sundström Poro-maa, I. (2004). Altered sensitivity to alcohol in the late luteal phase among patients with premenstrual dysphoric disorder. Psychoneuroen-docrinology 29, 767-777.
163. Osterlund, M. K., Gustafsson, J. A., Keller, E., and Hurd, Y. L. (2000). Estrogen receptor β (ERβ) messenger ribonucleic acid (mRNA) expression within the human fore-brain: distinct distribution pattern to ERβ mRNA. J. Clin. Endocrinol. Metab. 85, 3840-3846.
164. Padberg, F., di Michele, F., Zwanzger, P., Romeo, E., Bernardi, G., Schüle, C., Baghai, T. C., Ella, R., Pasini, A., and Rupprecht, R. (2002). Plasma concentrations of neuroac-tive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Neuropsychopharmacology 27, 874-878.
165. Papadopoulos, V. (2011). From benzo-diazepines to peripheral and brain steroid biosynthesis. Pharmacol. Res. 64, 330-332.
166. Papadopoulos, V., Baraldi, M., Guilarte, T. R., Knudsen, T. B., Lacapère, J. J., Lindemann, P., Norenberg, M. D., Nutt, D., Weizman, A., Zhang, M. R., and Gavish, M. (2006). Translo-cator protein (18kDa): new nomenclature for the peripheral-type ben-zodiazepine receptor based on its structure and molecular function. Trends Pharmacol. Sci. 27, 402-409.
167. Paris, J. J., Chittur, S. V., Tine, J. A., and Frye, C. A. (2011). Paced mating enhances expression of hormonal and trophic factors in the midbrain of female rats. Genes Brain Behav.
168. Patchev, V. K., and Almeida, O. F. (1996). Gonadal steroids exert facilitating and " buffering" effects on glucocorticoid-mediated transcrip-tional regulation of corticotropin-releasing hormone and corticos-teroid receptor genes in rat brain. J. Neurosci. 16, 7077-7084.
169. Patchev, V. K., Hassan, A. H., Holsboer, D. F., and Almeida, O. F. (1996). The neurosteroid tetrahy- droprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcrip tion in the rat hypothalamus. Neuropsychopharmacology 15, 533-540.
170. Patchev, V. K., Shoaib, M., Holsboer, F., and Almeida, O. F. (1994). The neu-rosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. Neuroscience 62, 265-271.
171. Paul, S. M., and Purdy, R. H. (1992). Neuroactive steroids. FASEB J. 6, 2311-2322.
172. Pearlstein, T., Yonkers, K. A., Fayyad, R., and Gillespie, J. A. (2005). Pretreatment pattern of symptom expression in premenstrual dys-phoric disorder. J. Affect Disord. 85, 275-282.
173. Petralia, S. M., DeBold, J. F., and Frye, C. A. (2007). MK-801 infusions to the ventral tegmental area and ventromedial hypothalamus produce opposite effects on lordosis of hormone-primed rats. Pharmacol. Biochem. Behav. 86, 377-385.
174. Petralia, S. M., and Frye, C. A. (2006a). In the ventral tegmen-tal area, cyclic AMP mediates the actions of progesterone at dopamine type 1 receptors for lordosis of rats and hamsters. J. Neuroendocrinol. 18, 902-914.
175. Petralia, S. M., and Frye, C. A. (2006b). In the ventral tegmental area, G-proteins mediate proges-terone's actions at dopamine type 1 receptors for lordosis of rats and hamsters. Psychopharmacology (Berl.) 186, 133-142.
176. Petralia, S. M., Jahagirdar, V., and Frye, C. A. (2005). Inhibiting biosynthesis and/or metabolism of progestins in the ventral tegmental area attenuates lordosis of rats in behavioural oestrus. J. Neuroendocrinol. 17, 545-552.
177. Petralia, S. M., and Frye, C. A. (2004). In the ventral tegmental area, G-proteins and cAMP mediate the neurosteroid 3α,5α-THP's actions at dopamine type 1 receptors for lor-dosis of rats. Neuroendocrinology 80, 233-243.
178. Pfaff, D. W., Gerlach, J. L., McEwen, B. S., Ferin, M., Carmel, P., and Zimmerman, E. A. (1976). Autora-diographic localization of hormone-concentrating cells in the brain of the female rhesus monkey. J. Comp. Neurol. 170, 279-293.
179. Pleim, E. T., Baumann, J., and Barfield, R. J. (1991). A contributory role for midbrain progesterone in the facilitation of female sexual behavior in rats. Horm. Behav. 25, 19-28.
180. Pomerleau, C. S., Mehringer, A. M., Marks, J. L., Downey, K. K., and Pomerleau, O. F. (2000). Effects of menstrual phase and smoking abstinence in smokers with and without a history of major depressive disorder. Addict. Behav. 25, 483-497.
181. Purdy, R. H., Moore, P. H. Jr, Rao, P. N., Hagino, N., Yamaguchi, T., Schmidt, P., Rubinow, D. R., Morrow, A. L., and Paul, S. M. (1990). Radioimmunoassay of 3α-hydroxy-5α-pregnan-20-one in rat and human plasma. Steroids 55, 290-296.
182. Purdy, R. H., Morrow, A. L., Moore, P. H. Jr., and Paul, S. M. (1991). Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain. Proc. Natl. Acad. Sci. U.S.A. 88, 4553-4557.
183. Quiñones-Jenab, V., Minerly, A. C., Niy-omchia, T., Akahvan, A., Jenab, S., and Frye, C. A. (2008). Progesterone and allopregnanolone are induced by cocaine in serum and brain tissues of male and female rats. Pharmacol. Biochem. Behav. 89, 292-297.
184. Ramcharan, S., Love, E. J., Fick, G. H., and Goldfien, A. (1992). The epidemiology of premenstrual symptoms in a population-based sample of 2650 urban women: attributable risk and risk factors. J. Clin. Epidemiol. 45, 377-392.
185. Rapkin, A. J., Mikacich, J. A., Moatakef-Imani, B., and Rasgon, N. (2002). The clinical nature and formal diagnosis of premenstrual, postpar-tum, and perimenopausal affective disorders. Curr. Psychiatry Rep. 4, 419-428.
186. Rapkin, A. J., Morgan, M., Goldman, L., Brann, D. W., Simone, D., and Mahesh, V. B. (1997). Progesterone metabolite allopreg-nanolone in women with premenstrual syndrome. Obstet. Gynecol. 90, 709-714.
187. Read, J., Perry, B. D., Moskowitz, A., and Connolly, J. (2001). The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurode-velopmental model. Psychiatry 64, 319-345.
188. Reddy, D. S. (2002). The clinical potentials of endogenous neurosteroids. Drugs Today 38, 465-485.
189. Reddy, D. S. (2003). Pharmacology of endogenous neuroactive steroids. Crit. Rev. Neurobiol. 15, 197-234.
190. Reddy, D. S. (2004). Pharmacology of catamenial epilepsy. Methods Find Exp. Clin. Pharmacol. 26, 547-561.
191. Regier, D. A., Farmer, M. E., Rae, D. S., Locke, B. Z., Keith, S. J., Judd, L. L., and Goodwin, F. K. (1990). Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic CatchmentArea (ECA) Study. JAMA 264, 2511-2518.
192. Rhodes, M. E., and Frye, C. A. (2001). Inhibiting progesterone metabolism in the hippocampusof ratsinbehav-ioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors. Cogn. Affect. Behav. Neurosci. 1, 287-296.
193. Romeo, E., Ströhle, A., Spalletta, G., di Michele, F., Hermann, B., Hols-boer, F., Pasini, A., and Rupprecht, R. (1998). Effects of antidepressant treatment on neuroactive steroids in major depression. Am. J. Psychiatry 155, 910-913.
194. Rose, J. D. (1990). Tectoreticular neu-ronal activity associated with behavior and progesterone action during the induction of lordosis responding in hamsters. Abstr. Soc. Neurosci. 16, 924.
195. Rubin, R. T., Poland, R. E., Lesser, I. M., Winston, R. A., and Blodgett, A. L. (1987). Neuroendocrine aspects of primary endogenous depression. I. Cortisol secretory dynamics in patients and matched controls. Arch. Gen. Psychiatry 44, 328-336.
196. Rubinow, D. R., Hoban, M. C., Grover, G. N., Galloway, D. S., Roy-Byrne, P., Andersen, R., and Merriam, G. R. (1988). Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects. Am. J. Obstet. Gynecol. 158, 5-11.
197. Rupprecht, R., and Holsboer, F. (1999). Neuroactive steroids: mechanisms of action and neuropsychopharmaco-logical perspectives. Trends Neurosci. 22, 410-416.
198. Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T. C., Fan, J., Akula, N., Groyer, G., Adams, D., and Schumacher, M. (2010). Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug Discov. 9, 971-988.
199. Russo, S. J., Sun, W. L., Minerly, A. C., Weierstall, K., Nazarian, A., Festa, E. D., Niyomchai, T., Akhavan, A., Luine, V., Jenab, S., and Quiñones-Jenab, V. (2008). Progesterone attenuates cocaine-induced conditioned place preference in female rats. Brain Res. 1189, 229-235.
200. Sanders, D., Warner, P., Bäckström, T., and Bancroft, J. (1983). Mood, sexuality, hormones and the menstrual cycle. I. Changes in mood and physical state: description of subjects and method. Psychosom. Med. 45, 487-501.
201. Schmidt,P. J., Nieman,L. K., Danaceau, M. A., Adams, L. F., and Rubinow, D. R. (1998). Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N. Engl. J. Med. 33, 209-216.
202. Schmidt, P. J., Purdy, R. H., Moore, P. H. Jr., Paul, S. M., and Rubi-now, D. R. (1994). Circulating levels of anxiolytic steroids in the luteal phase in women with premenstrual syndrome and in control subjects. J. Clin. Endocrinol. Metab. 79, 1256-1260.
203. Schüle, C., di Michele, F., Baghai, T., Romeo, E., Bernardi, G., Zwanzger, P., Padberg, F., Pasini, A., and Rupprecht, R. (2003). Influence of sleep deprivation on neuroactive steroids in major depression. Neu-ropsychopharmacology 28, 577-581.
204. Schüle, C., Eser, D., Baghai, T. C., Nothdurfter, C., Kessler, J. S., and Rupprecht, R. (2011). Neuroactive steroids in affective disorders: target for novel antidepressant or anxiolytic drugs? Neuroscience 191, 55-77.
205. Schwartz-Giblin, S., and Pfaff, D. W. (1986). Hypothalamic output controlling reticulospinal and vestibu-lospinal systems important for emotional behavior. Int. J. Neurol. 1986, 89-110.
206. Seeman, M. V. (1997). Psychopathol-ogy in women and men: focus on female hormones. Am. J. Psychiatry 154, 1641-1647.
207. Seippel, L., and Bäckström, T. (1998). Luteal-phase estradiol relates to symptom severity in patients with premenstrual syndrome. J. Clin. Endocrinol. Metab. 83, 1988-1992.
208. Selye, H. (1941). On the hormonal activity of a steroid compound. Science 94, 94.
209. Serra, M., Pisul, M. G., Dazzi, L., Purdy, R. H., and Biggio,G. (2002). Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine. J. Psychopharma-col. 16, 133-138.
210. Shirayama, Y., Hashimoto, K., Suzuki, Y., and Higuchi, T. (2002). Correlation of plasma neurosteroid levels to the severity of negative symptoms in male patients with schizophrenia. Schizophr. Res. 58, 69-74.
211. Shughrue, P. J., Lane, M. V., and Merchenthaler, I. (1997). Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study. Endocrinology 138, 5476-5484.
212. Sinha, R., Fox, H., Hong, K. I., Sofuoglu, M., Morgan, P. T., and Bergquist, K. T. (2007). Sex steroid hormones, stress response, and drug craving in cocaine-dependent women: implications for relapse susceptibility. Exp. Clin. Psychopharmacol. 15, 445-452.
213. Sinnott, R. S., Mark, G. P., and Finn, D. A. (2002). Reinforcing effects of the neurosteroid allopregnanolone in rats. Pharmacol. Biochem. Behav. 72, 923-929.
214. Soares, C. N., and Cohen, L. S. (2001). The perimenopause, depressive disorders, and hormonal variability. Sao Paulo Med. J. 119, 78-83.
215. Sofuoglu, M., Babb, D. A., and Hat-sukami, D. K. (2002). Effects of progesterone treatment on smoked cocaine response in women. Pharmacol. Biochem. Behav. 72, 431-435.
216. Sofuoglu, M., Dudish-Poulsen, S., Nelson, D., Pentel, P. R., and Hat-sukami, D. K. (1999). Sex and menstrual cycle differences in the subjective effects from smoked cocaine in humans. Exp. Clin. Psychopharma-col. 7, 274-283.
217. Sofuoglu, M., Mitchell, E., and Kosten, T. R. (2004). Effects of progesterone treatment on cocaine responses in male and female cocaine users. Pharmacol. Biochem. Behav. 78, 699-705.
218. Steffensen, S. C., Svingos,A. L., Pickel,V. M., and Henriksen,S. J. (1998). Elec-trophysiological characterization of GABAergic neurons in the ventral tegmental area. J. Neurosci. 18, 8003-8015.
219. Ströhle, A., Romeo, E., di Michele, F., Pasini, A., Hermann, B., Gajew-sky, G., Holsboer, F., and Rup-precht, R. (2003). Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder: preliminary results. Arch. Gen. Psychiatry 60, 161-168.
220. Sumida, K., Walf, A. A., and Frye, C. A. (2005). Progestin-facilitated lordosis of hamsters may involve dopamine-like type 1 receptors in the ventral tegmental area. Behav. Brain Res. 161, 1-7.
221. Sundström, I., Andersson, A., Nyberg, S., Ashbrook, D., Purdy, R. H., and Bäckström, T. (1998). Patients with premenstrual syndrome have a different sensitivity to a neu-roactive steroid during the menstrual cycle compared to control subjects. Neuroendocrinology 67, 126-138.
222. Sundström, I., Ashbrook, D., and Bäck-ström, T. (1997a). Reduced ben-zodiazepine sensitivity in patients with premenstrual syndrome: a pilot study. Psychoneuroendocrinology 22, 25-38.
223. Sundström, I., Nyberg, S., and Bäck-ström, T. (1997b). Patients with premenstrual syndrome have reduced sensitivity to midazolam compared to control subjects. Neuropsy-chopharmacology 17, 370-381.
224. Sundström, I., and Bäckström, T. (1998a). Citalopram increases preg-nanolone sensitivity in patients with premenstrual syndrome: an open trial. Psychoneuroendocrinology 23, 73-88.
225. Sundström, I., and Bäckström, T. (1998b). Patients with premenstrual syndrome have decreased saccadic eye velocity compared to control subjects. Biol. Psychiatry 44, 755-764.
226. Sundström, I., Bäckström, T., Wang, M., Olsson, T., Seippel, L., and Bixo, M. (1999). Premenstrual syndrome, neuroactive steroids and the brain. Gynecol. Endocrinol. 13, 206-220.
227. Sveindóttir, H., and Bäckström, T. (2000). Prevalence of menstrual cycle symptom cyclicity and premenstrual dysphoric disorder in a random sample of women using and not using oral contraceptives. Acta Obstet. Gynecol. Scand. 79, 405-413.
228. Tait, G. R., McManus, K., Bellavance, F., Lara, N., Chrapko, W., and Le Mellédo, J. M. (2002). Neuroac-tive steroid changes in response to challenge with the paγnicogenic agent pentagastrin. Psychoneuroen-docrinology 27, 417-429.
229. Taylor, S. E., Klein, L. C., Lewis, B. P., Gruenewald, T. L., Gurung, R. A., and Updegraff, J. A. (2000). Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight. Psychol. Rev. 107, 411-429.
230. Townsend, K. A., and Marlowe, K. F. (2004). Relative safety and efficacy of finasteride for treatment of hirsutism. Ann. Pharmacother. 38, 1070-1073.
231. Usall, J., Suarez, D., Haro, J. M., and SOHO Study Group. (2007). Gender differences in response to antipsy-chotic treatment in outpatients with schizophrenia. Psychiatry Res 153, 225-231.
232. Uzunova, V., Sampson, L., and Uzunov, D. P. (2006). Relevance of endogenous 3α-reduced neurosteroids to depression and antidepressant action. Psychopharmacology (Berl.) 186, 351-361.
233. Uzunova, V., Sheline, Y., Davis, J. M., Rasmusson, A., Uzunov, D. P., Costa, E., and Guidotti, A. (1998). Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxam-ine. Proc. Natl. Acad. Sci. U.S.A. 95, 3239-3244.
234. Uzunova, V., Wrynn, A. S., Kin-nunen, A., Ceci, M., Kohler, C., and Uzunov, D. P. (2004). Chronic antidepressants reverse cerebrocor-tical allopregnanolone decline in the olfactory-bulbectomized rat. Eur. J. Pharmacol. 486, 31-34.
235. Verleye, M.,Akwa,Y., Liere, P., Ladurelle, N., Pianos, A., Eychenne, B., Schumacher, M., and Gillardin, J. M. (2005). The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neuros-teroid levels in rat brain. Pharmacol. Biochem. Behav. 82, 712-720.
236. Walf, A. A., and Frye, C. A. (2006). A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior. Neuropsychopharmacology 31, 1097-1111.
237. Walf, A. A., Paris, J. J., Llaneza, D. C., and Frye, C. A. (2011). I. Levels of 5(-reduced progesterone metabolite in the midbrain account for variability in reproductive behavior of middle-aged female rats. Brain Res. 1379, 137-148.
238. Walf, A. A., Sumida, K., and Frye, C. A. (2006). Inhibiting 5α-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats. Psychopharmacology (Berl.) 186, 302-311.
239. Wang, M., Bäckström, T., Sundström, I., Wahlström, G., Olsson, T., Zhu, D., Johansson, I. M., Björn, I., and Bixo, M. (2001). Neuroactive steroids and central nervous system disorders. Int. Rev. Neurobiol. 46, 421-459.
240. Wang, M., Seippel, L., Purdy, R. H., and Bäckström, T. (1996). Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, preg-nenolone sulfate, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one. J. Clin. Endocrinol. Metab. 81, 1076-1082.
241. Warembourg, M. (1978). Radioauto-graphic study of the rat brain, uterus and vagina after [3H]R-5020 injection. Mol. Cell. Endocrinol. 12, 67-79.
242. Weir, C. J., Ling, A. T., Belelli, D., Wild-smith, J. A., Peters, J. A., and Lambert, J. J. (2004). The interaction of anaesthetic steroids with recombi-nant glycine and GABAA receptors. Br. J. Anaesth. 92, 704-711.
243. Weissman, M. M., and Klerman, G. L. (1977). Sex differences and the epidemiology of depression. Arch. Gen. Psychiatry 34, 98-111.
244. Wittchen, H. U., and Hoyer, J. (2001). Generalized anxiety disorder: nature and course. J. Clin. Psychiatry 62, 15-19.
245. Wu, G., Kaper, J. M., and Jaspars, E. M. (1991). Replication of cucumber mosaic virus satellite RNA in vitro by an RNA-dependent RNA poly-merase from virus-infected tobacco. FEBS Lett. 292, 213-216.
246. Xie, W., and Evans, R. M. (2002). Pharmaceutical use of mouse models humanized for the xenobiotic receptor. Drug Discov. Today 7, 509-515.
247. Young, E. A., Midgley, A. R., Carlson, N. E., and Brown, M. B. (2000). Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch. Gen. Psychiatry 57, 1157-1162.
248. Zhu, Y., Bond, J., and Thomas, P. (2003). Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc. Natl. Acad. Sci. U.S.A. 100, 2237-2242.
249. Zwanzger, P., Eser, D., Padberg, F., Baghai, T. C., Schüle, C., Rupprecht, R., di Michele, F., Romeo, E., Pasini, A., and Ströhle, A. (2004). Neu-roactive steroids are not affected by panic induction with 50 microg cholecystokinin-tetrapeptide (CCK-4) in healthy volunteers. J. Psychiatr. Res. 38, 215-217.