Relevance of endogenous 3α-reduced neurosteroids to depression and antidepressant action

Psychopharmacology

Volumn 186, Issue 3, 2006, Pages 351-361

  Uzunova, Veska ^a   Sampson, Luther ^a   Uzunov, Doncho P ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Allopregnanolone; Neuroactive steroids; Pregnanolone; SSRI

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 3ALPHA,21 DIHYDROXY 5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; 4' CHLORODIAZEPAM; 5ALPHA PREGNANE 3,20 DIONE; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; BICUCULLINE; CLOMIPRAMINE; DESIPRAMINE; ELTANOLONE; FLUOXETINE; IMIPRAMINE; INDOMETACIN; LITHIUM; MAPROTILINE; MONOAMINE OXIDASE INHIBITOR; MUSCIMOL; NEUROSTEROID; NORFLUOXETINE; NORTRIPTYLINE; PAROXETINE; PROGESTERONE DERIVATIVE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRICYCLIC ANTIDEPRESSANT AGENT; UNINDEXED DRUG; VENLAFAXINE; VILOXAZINE;

ANIMAL BEHAVIOR; DEPRESSION; DISEASE MODEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG EFFECT; FORCED SWIMMING TEST; GABAERGIC SYSTEM; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; NEUROENDOCRINOLOGY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGESTERONE METABOLISM; PSYCHOPHARMACOLOGY; REVIEW; RIGHTING REFLEX; SOCIAL ISOLATION; STEROID BLOOD LEVEL; ANIMAL; METABOLISM;

ANIMALS; ANTIDEPRESSIVE AGENTS; DEPRESSION; HUMANS; PREGNANOLONE; SEROTONIN UPTAKE INHIBITORS;

EID: 33744503400     PISSN: 00333158     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00213-005-0201-6     Document Type: Review

References (90)

1. Akwa Y, Purdy RH, Koob GF, Britton KT (1999) The amygdala mediates the anxiolytic-like effect of the neurosteroid allopregnanolone in rat. Behav Brain Res 106:119-125
2. Baghai TC, di Michele F, Schuele C, Eser D, Zwanzger P, Pasini A, Romeo E, Rupprecht R (2005) Plasma concentrations of neuroactive steroids before and after electroconvulsive therapy in major depression. Neuropsychopharmacology 30:1181-1186
3. Baulieu EE (1998) Neurosteroids: a novel function of the brain. Psychoneuroendocrinology 23:963-987
4. Baulieu EE, Robel P, Schumacher M (2001) Neurosteroids: beginning of the story. Int Rev Neurobiol 46:1-32
5. Bixo M, Andersson A, Winblad B, Purdy RH, Backstrom T (1997) Progesterone, 5alpha-pregnane-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
6. Cryan JF, McGrath C, Leonard BE, Norman TR (1998) Combining pindolol and paroxetine in an animal model of chronic antidepressant action - can early onset of action be detected? Eur J Pharmacol 352:23-28
7. Cryan JF, McGrath C, Leonard BE, Norman TR (1999) Onset of the effects of the 5-HT1A antagonist, WAY-100635, alone, and in combination with paroxetine, on olfactory bulbectomy and 8-OH-DPAT-induced changes in the rat. Pharmacol Biochem Behav 63:333-338
8. Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23:238-245
9. Czlonkowska AI, Zienowicz M, Bidzinski A, Maciejak P, Lehner M, Taracha E, Wislowska A, Plaznik A (2003) The role of neurosteroids in the anxiolytic, antidepressive- and anticonvulsive effects of selective serotonin reuptake inhibitors. Med Sci Monit 9:270-275
10. Davis M (1992) The role of the amygdala in conditioned fear. In: Aggleton JP (ed) The amygdala: neurobiological aspects of emotion. Wiley-Liss, New York, pp 255-305
11. Dong E, Matsumoto K, Uzunova V, Sugaya I, Takahata H, Nomura H, Watanabe H, Costa E, Guidotti A (2001) Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation. Proc Natl Acad Sci U S A 98:2849-2854
12. Drevets WC (2000) Neuroimaging of mood disorders. Biol Psychiatry 48:813-829
13. Dubrovsky B (2000) The specificity of stress responses to different nocuous stimuli: neurosteroids and depression. Brain Res Bull 51:443-455
14. Dubrovsky BO (2005) Steroids, neuroactive steroids and neurosteroids in psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 29:169-192
15. Eisensamer B, Rammes G, Gimpl G, Shapa M, Ferrari U, Hapfelmeier G, Bondy B, Parsons C, Gilling K, Zieglgansberger W, Holsboer F, Rupprecht R (2003) Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor. Mol Psychiatry 8:994-1007
16. A receptors. Nat Rev Neurosci 6:215-229
17. Frye CA, Walf AA (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
18. Frye CA, Walf AA (2004) Hippocampal 3alpha, 5alpha-THP may alter depressive behavior of pregnant and lactating rats. Pharmacol Biochem Behav 78:531-540
19. Frye CA, Walf AA, Rhodes ME, Harney JP (2004) Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase. Brain Res 1004:116-124
20. Garzon J, Fuentes JA, Del Rio J (1979) Antidepressants selectively antagonize the hyperactivity induced in rats by long-term isolation. Eur J Pharmacol 59:293-296
21. Gasior M, Carter RB, Witkin JM (1999) Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders. Trends Pharmacol Sci 20:107-112
22. Genazzani AR, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, Nappi RE, Luisi S, Palumbo M, Purdy RH, Luisi M (1998) Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab 83:2099-2103
23. Goodnick PJ, Goldstein BJ (1998) Selective serotonin reuptake inhibitors in affective disorders II. Efficacy and quality of life. J Psychopharmacol 12:S21-S54
24. Griffin LD, Mellon SH (1999) Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci U S A 96:13512-13517
25. Griffin LD, Conrad SC, Mellon SH (2001) Current perspectives on the role of neurosteroids in PMS and depression. Int Rev Neurobiol 46:479-492
26. Guidotti A, Costa E (1998) Can the antidysphoric and anxiolytic profiles of selective serotonin reuptake inhibitors be related to their ability to increase brain 3 alpha, 5 alpha-tetrahydroprogesterone (allopregnanolone) availability? Biol Psychiatry 44:865-873
27. 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 5α-dihydroprogesterone in psychiatric disorders. Brain Res Rev 37:110-115
28. Jesberger JA, Richardson JS (1988) Brain output dysregulation induced by olfactory bulbectomy: an approximation in the rat of major depressive disorder in humans? Int J Neurosci 38:241-265
29. 3H]5 alpha-dihydroprogesterone by rat brain and pituitary and effects of estradiol and time: tissue concentration of progesterone itself or specific metabolites? Endocrinology 104:1418-1425
30. Kelly JP, Wrynn AS, Leonard BE (1997) The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 74:299-316
31. Kendell SF, Krystal JH, Sanacora G (2005) GABA and glutamate systems as therapeutic targets in depression and mood disorders. Expert Opin Ther Targets 9:153-168
32. Khisti RT, Chopde CT (2000) Serotonergic agents modulate antidepressant-like effect of the neurosteroid 3α-hydroxy-5α- pregnan-20-one in mice. Brain Res 865:291-300
33. Khisti RT, Chopde CT, Jain SP (2000) Antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in mice forced swim test. Pharmacol Biochem Behav 67:137-143
34. Kim YS, Zhang H, Kim HY (2000) Profiling neurosteroids in cerebrospinal fluids and plasma by gas chromatography/electron capture negative chemical ionization mass spectrometry. Anal Biochem 277:187-195
35. Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF (2002) Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry 7:S71-S80
36. Lacroix C, Fiet J, Benais JP, Gueux B, Bonete R, Villette JM, Gourmel B, Dreux C (1987) Simultaneous radioimmunoassay of progesterone, androst-4-enedione, pregnenolone, dehydroepiandrosterone and 17-hydroxyprogesterone in specific regions of human brain. J Steroid Biochem 28:317-325
37. A receptor function. Trends Pharmacol Sci 16:295-303
38. Lambert JJ, Belelli D, Peden DR, Vardy AW, Peters JA (2003) Neurosteroid modulation of GABAA receptors. Prog Neurobiol 71:67-80
39. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155-184
40. Lucki I (1997) The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 8:523-532
41. Lumia AR, Teicher MH, Salchli F, Ayers E, Possidente B (1992) Olfactory bulbectomy as a model for agitated hyposerotonergic depression. Brain Res 587:181-185
42. 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
43. Martinez-Mota L, Contreras CM, Saavedra M (1999) Progesterone reduces immobility in rats forced to swim. Arch Med Res 30:286-289
44. Matsumoto K, Uzunova V, Pinna G, Taki K, Uzunov DP, Watanabe H, Mienville J-M, Guidotti A, Costa E (1999) Permissive role of brain allopregnanolone content in the regulation of pentobarbital-induced righting reflex loss. Neuropharmacology 38:955-963
45. Mellon SH, Griffin LD (2002) Neurosteroids: biochemistry and clinical significance. Trends Endocrinol Metab 13:35-43
46. Molina-Hernandez M, Tellez-Alcantara NP (2001) Antidepressant-like actions of pregnancy, and progesterone in Wistar rats forced to swim. Psychoneuroendocrinology 26:479-491
47. Molina-Hernandez M, Tellez-Alcantara NP, Garcia JP, Lopez JI, Jaramillo MT (2004) Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim. Prog Neuropsychopharmacol Biol Psychiatry 28:1337-1345
48. Molina-Hernandez M, Tellez-Alcantara NP, Garcia JP, Lopez JI, Jaramillo MT (2005) Antidepressant-like actions of intra-accumbens infusions of allopregnanolone in ovariectomized Wistar rats. Pharmacol Biochem Behav 80:401-409
49. Murphy PBE, Steinberg SI, Hu FY, Allison CM (2001) Neuroactive ring A-reduced metabolites of progesterone in human plasma during pregnancy: elevated levels of 5 alpha-dihydroprogesterone in depressed patients during the latter half of pregnancy. J Clin Endocrinol Metab 86:5981-5987
50. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002) Neurobiology of depression. Neuron 34:13-25
51. O'Connor WT, Earley B, Leonard BE (1985) Antidepressant properties of the triazolobenzodiazepines alprazolam and adinazolam: studies in the olfactory bulbectomized rat model of depression. Brain J Clin Pharmacol 19:45S-56S
52. Pacher P, Kohegyi E, Kecskemeti V, Furst S (2001) Current trends in the development of new antidepressants. Curr Med Chem 8:89-100
53. Padberg F, di Michele F, Zwanzger P, Romeo E, Bernardi G, Schuele C, Baghai TC, Ella R, Pasini A, Rupprecht R (2002) Plasma concentrations of neuroactive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Neuropsychopharmacology 27:874-878
54. Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I (1999) Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology 147:162-167
55. Paul SM, Purdy RH (1992) Neuroactive steroids. FASEB J 6:2311-2322
56. Pause BM, Miranda A, Goeder R, Aldenhoff JB, Ferstl R (2001) Reduced olfactory performance in patients with major depression. J Psychiatr Res 35:271-277
57. Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K (2000) Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J 351:67-77
58. Petit-Demouliere B, Chenu F, Bourin M (2005) Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology 177:245-255
59. A receptor agonist muscimol. Neuropharmacology 39:440-448
60. Pinna G, Dong E, Matsumoto K, Costa E, Guidotti A (2003) In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine. Proc Natl Acad Sci U S A 100:2035-2040
61. Pinna G, Costa E, Guidotti A (2004) Fluoxetine and norfluoxetine stereospecifically facilitate pentobarbital sedation by increasing neurosteroids. Proc Natl Acad Sci U S A 101:6222-6225
62. Pisu MG, Serra M (2004) Neurosteroids and neuroactive drugs in mental disorders. Life Sci 74:3181-3197
63. Purdy RH, Moore PH Jr, Rao PN, Hagino N, Yamaguchi T, Schmidt P, Rubinow DR, Morrow AL, Paul SM (1990) Radioimmunoassay of 3 alpha-hydroxy-5 alpha-pregnan-20-one in rat and human plasma. Steroids 55:290-296
64. Reddy DS (2002) The clinical potentials of endogenous neurosteroids. Drugs Today 38:465-485
65. Reddy DS (2003a) Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions? Trends Pharmacol Sci 24:103-106
66. Reddy DS (2003b) Pharmacology of endogenous neuroactive steroids. Crit Rev Neurobiol 15:197-234
67. Romeo E, Stroehle 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
68. Rupprecht R (2003) Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties. Psychoneuroendocrinology 28:139-168
69. Rupprecht R, Holsboer F (1999a) Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci 22:410-416
70. Rupprecht R, Holsboer F (1999b) Neuropsychopharmacological properties of neuroactive steroids. Steroids 64:83-91
71. Rupprecht R, Stroehle A, Hermann B, di Michele F, Spalletta G, Pasini A, Holsboer F, Romeo E (1998) Neuroactive steroid concentrations following metyrapone administration in depressed patients and healthy volunteers. Biol Psychiatry 44:912-914
72. Rupprecht R, di Michele F, Hermann B, Stroehle A, Lancel M, Romeo E, Holsboer F (2001) Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology. Brain Res Rev 37:59-67
73. Schuele C, di Michele F, Baghai T, Romeo E, Bernardi G, Zwanzger P, Padberg F, Pasini A, Rupprecht R (2003) Influence of sleep deprivation on neuroactive steroids in major depression. Neuropsychopharmacology 28:577-581
74. Schuele C, di Michele F, Baghai T, Romeo E, Bernardi G, Zwanzger P, Padberg F, Pasini A, Rupprecht R (2004) Neuroactive steroids in responders and nonresponders to sleep deprivation. Ann N Y Acad Sci 1032:216-223
75. A receptor function in rat brain. J Neurochem 75:732-740
76. Serra M, Pisu MG, Muggironi M, Parodo V, Papi G, Sari R, Dazzi L, Spiga F, Purdy RH, Biggio G (2001) Opposite effects of short- versus long-term administration of fluoxetine on the concentrations of neuroactive steroids in rat plasma and brain. Psychopharmacology 158:48-54
77. Stoffel-Wagner B (2001) Neurosteroid metabolism in the human brain. Eur J Endocrinol 145:669-679
78. Stroehle A, Romeo E, Hermann B, Pasini A, Spalletta G, di Michele F, Holsboer F, Rupprecht R (1999) Concentrations of 3α-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Biol Psychiatry 45:274-277
79. Stroehle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R (2000) Fluoxetine decreases concentrations of 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) in major depression. J Psychiatr Res 34:183-186
80. Tichomirowa MA, Keck ME, Schneider HJ, Paez-Pereda M, Renner U, Holsboer F, Stella GK (2005) Endocrine disturbances in depression. J Endocrinol Invest 28:89-99
81. Trauger JW, Jiang A, Stearns BA, LoGrasso PV (2002) Kinetics of allopregnanolone formation catalyzed by human 3 alpha-hydroxysteroid dehydrogenase type III (AKR1C2). Biochemistry 41:13451-13459
82. Uzunov DP, Cooper TB, Costa E, Guidotti A (1996) Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Proc Natl Acad Sci U S A 93:12599-12604
83. 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
84. Uzunova V, Ceci M, Kohler C, Uzunov DP, Wrynn AS (2003) Region-specific dysregulation of allopregnanolone brain content in the olfactory bulbectomized rat model of depression. Brain Res 976:1-8
85. Uzunova V, Wrynn AS, Kinnunen A, Ceci M, Kohler C, Uzunov DP (2004) Chronic antidepressants reverse cerebrocortical allopregnanolone decline in the olfactory-bulbectomized rat. Eur J Pharmacol 486:31-34
86. van Broekhoven F, Verkes RJ (2003) Neurosteroids in depression: a review. Psychopharmacology 165:97-110
87. Wang MD, Wahlstrom G, Backstrom T (1997) The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion. J Steroid Biochem Mol Biol 62:299-306
88. Wong ML, Licinio J (2001) Research and treatment approaches to depression. Nat Rev Neurosci 2:343-351
89. Wong ML, Licinio J (2004) From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat Rev Drug Discov 3:136-151
90. Zorumski CF, Mennerick S, Isenberg KE, Covey DF (2000) Potential clinical use of neuroactive steroids. Curr Opin Investig Drugs 1:360-369