Emerging experimental therapeutics for bipolar disorder: Clues from the molecular pathophysiology

Molecular Psychiatry

Volumn 9, Issue 8, 2004, Pages 756-776

  Quiroz, J A ^a   Singh, J ^a   Gould, T D ^a   Denicoff, K D ^a   Zarate Jr , C A ^a   Manji, H K ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

Corticotropin releasing factor; Depression; Felbamate; Glucocorticoids; Glutamate; Mania; Memantine; Mitochondria; Neuroplasticity; NMDA; Riluzole; Zinc

Indexed keywords

11BETA (1,3 BENZODIOXOL 5 YL) 17BETA HYDROXY 17ALPHA (1 PROPYNYL)ESTRA 4,9 DIEN 3 ONE; 2 AMINOTHIAZOLE DERIVATIVE; 4 [4 (3 FLUOROPHENYL) 1,2,3,6 TETRAHYDRO 1 PYRIDINYL] 2 [N ETHYL N (4 ISOPROPYL 2 METHYLTHIOPHENYL)AMINO] 6 METHYLPYRIMIDINE; 8 (2,4 DICHLOROPHENYL) 4 [2 METHOXY 1 (METHOXYMETHYL)ETHYLAMINO] 2,7 DIMETHYLPYRAZOLO[1,5 A][1,3,5]TRIAZINE; AL 082D06; AMINOGLUTETHIMIDE; ANTALARMIN; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ATYPICAL ANTIPSYCHOTIC AGENT; BUTYL[2,5 DIMETHYL 7 (2,4,6 TRIMETHYLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 4 YL]ETHYLAMINE; CORTICOSTEROID; CORTICOTROPIN; CORTICOTROPIN RELEASING FACTOR ANTAGONIST; DESIPRAMINE; DEXAMETHASONE; DIZOCILPINE; DMP 695; FLUOXETINE; GLUCOCORTICOID; GLUCOCORTICOID ANTAGONIST; HALOPERIDOL; HYDROCORTISONE; IMIPRAMINE; KETOCONAZOLE; LITHIUM; LY 392098; LY 451616; METYRAPONE; MIFEPRISTONE; N METHYL DEXTRO ASPARTIC ACID; NBI 35965; NEUROLEPTIC AGENT; ORG 34116; ORG 34850; PRASTERONE; PSYCHOTROPIC AGENT; R 121919 5; RILUZOLE; SPIRONOLACTONE; SSR 125543 A; STEROID; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AGITATION; APLASTIC ANEMIA; BEHAVIOR DISORDER; BIPOLAR DISORDER; CELL FUNCTION; CLINICAL TRIAL; DEPRESSION; DISEASE EXACERBATION; DRUG EFFECT; DRUG SAFETY; ELECTRIC SHOCK; ENZYME ACTIVITY; EXPERIMENTAL THERAPY; HUMAN; HYPOMANIA; MANIA; MEDICAL LITERATURE; MITOCHONDRION; MOLECULAR MECHANICS; MOOD DISORDER; MORBIDITY; MORTALITY; NAUSEA; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PARESTHESIA; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SLEEP DISORDER; TOXIC HEPATITIS; VOMITING; XEROSTOMIA;

ANTIMANIC AGENTS; ANTIPSYCHOTIC AGENTS; BIPOLAR DISORDER; BRAIN; HUMANS; MOOD DISORDERS; NEURONAL PLASTICITY; STRESS, PSYCHOLOGICAL;

EID: 4243165658     PISSN: 13594184     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.mp.4001521     Document Type: Review

References (246)

1. Goodwin FK, Ghaemi SN. The course of bipolar disorder and the nature of agitated depression. Am J Psychiatry 2003; 160: 2077-2079.
2. Gould TD, Quiroz J, Singh J, Zarate Jr CA, Manji HK. Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers. Mol Psychiatry 2004.
3. Schulze TG, McMahon FJ. Genetic linkage and association studies in bipolar affective disorder: a time for optimism. Am J Med Genet 2003; 123C: 36-47.
4. Sheline YI. Neuroimaging studies of mood disorder effects on the brain. Biol Psychiatry 2003; 54: 338-352.
5. Drevets WC. Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog Brain Res 2000; 126: 413-431.
6. Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001; 7: 541-547.
7. Drevets WC. Neuroimaging abnormalities in the amygdala in mood disorders. Ann NY Acad Sci 2003; 985: 420-444.
8. Manji H, Duman R. Impairments of neuroplasticity and cellular resilience in severe mood disorder: implications for the development of novel therapeutics. Psychopharmacol Bull 2001; 35: 5-49.
9. Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001; 11: 240-249.
10. Strakowski SM, Adler CM, DelBello MP. Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder? Bipolar Disord 2002; 4: 80-88.
11. Beyer JL, Krishnan KR. Volumetric brain imaging findings in mood disorders. Bipolar Disord 2002; 4: 89-104.
12. Cotter D, Mackay D, Landau S, Kerwin R, Everall I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 2001; 58: 545-553.
13. Rajkowska G. Cell pathology in bipolar disorder. Bipolar Disord 2002; 4: 105-116.
14. Lenox RH, Gould TD, Manji HK. Endophenotypes in bipolar disorder. Am J Med Genet 2002; 114: 391-406.
15. Carmelli D, Reed T, DeCarli C. A bivariate genetic analysis of cerebral white matter hyperintensities and cognitive performance in elderly male twins. Neurobiol Aging 2002; 23: 413-420.
16. Taylor WD, Payne ME, Krishnan KR, Wagner HR, Provenzale JM, Steffens DC et al. Evidence of white matter tract disruption in MRI hyperintensities. Biol Psychiatry 2001; 50: 179-183.
17. Lee SH, Payne ME, Steffens DC, McQuoid DR, Lai TJ, Provenzale JM et al. Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression. Biol Psychiatry 2003; 54: 529-533.
18. Mezzapesa DM, Rocca MA, Pagani E, Comi G, Filippi M. Evidence of subtle gray-matter pathologic changes in healthy elderly individuals with nonspecific white-matter hyperintensities. Arch Neurol 2003; 60: 1109-1112.
19. Stoll AL, Renshaw PF, Yurgelun-Todd DA, Cohen BM. Neuroimaging in bipolar disorder: what have we learned? Biol Psychiatry 2000; 48: 505-517.
20. D'Sa C, Duman R. Antidepressants and neuroplasticity. Bipolar Disorder 2002; 4: 183.
21. Lopez JF, Chalmers DT, Little KY, Watson SJ. AE Bennett Research Award. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression. Biol Psychiatry 1998; 43: 547-573.
22. Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000; 57: 925-935.
23. McEwen BS. Stress and hippocampal plasticity. Annu Rev Neurosci 1999; 22: 105-122.
24. Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000; 21: 55-89.
25. Sapolsky RM. Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1996; 1: 1-19.
26. Gould E, Tanapat P, Rydel T, Hastings N. Regulation of hippocampal neurogenesis in adulthood. Biol Psychiatry 2000; 48: 715-720.
27. Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature 1997; 386: 493-495.
28. van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266-270.
29. Cameron HA, McKay RD. Restoring production of hippocampal neurons in old age. Nat Neurosci 1999; 2: 894-897.
30. Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104-9110.
31. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 2000; 75: 1729-1734.
32. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805-809.
33. Vollmayr B, Simonis C, Weber S, Gass P, Henn F. Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry 2003; 54: 1035-1040.
34. Rupniak NM. Elucidating the antidepressant actions of substance P (NK1 receptor) antagonists. Curr Opin Invest Drugs 2002; 3: 257-261.
35. Morcuende S, Gadd CA, Peters M, Moss A, Harris EA, Sheasby A et al. Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice. Eur J Neurosci 2003; 18: 1828-1836.
36. Sheline YI, Sanghavi M, Mintun MA, Gado MH. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 1999; 19: 5034-5043.
37. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 2003; 100: 1387-1392.
38. Sheline YI, Gado MH, Kraemer HC. Untreated depression and hippocampal volume loss. Am J Psychiatry 2003; 160: 1516-1518.
39. Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD. Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biol Psychiatry 2003; 54: 693-702.
40. Lyons DM, Yang C, Sawyer-Glover AM, Moseley ME, Schatzberg AF. Early life stress and inherited variation in monkey hippocampal volumes. Arch Gen Psychiatry 2001; 58: 1145-1151.
41. Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci 2002; 5: 1242-1247.
42. Wellman CL. Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. J Neurobiol 2001; 49: 245-253.
43. Lyons DM. Stress, depression, and inherited variation in primate hippocampal and prefrontal brain development. Psychopharmacol Bull 2002; 36: 27-43.
44. Sonino N, Fava GA. Psychiatric disorders associated with Cushing's syndrome. Epidemiology, pathophysiology and treatment. CNS Drugs 2001; 15: 361-373.
45. Krystal A, Krishnan KR, Raitiere M, Poland R, Ritchie JC, Dunnick NR et al. Differential diagnosis and pathophysiology of Cushing's syndrome and primary affective disorder. J Neuropsychiatry Clin Neurosci 1990; 2: 34-43.
46. Kelly WF, Kelly MJ, Faragher B. A prospective study of psychiatric and psychological aspects of Cushing's syndrome. Clin Endocrinol (Oxf) 1996; 45: 715-720.
47. Starkman MN, Giordani B, Gebarski SS, Berent S, Schork MA, Schteingart DE. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease. Biol Psychiatry 1999; 46: 1595-1602.
48. Simmons NE, Alden TD, Thorner MO, Laws Jr ER. Serum cortisol response to transsphenoidal surgery for Cushing disease. J Neurosurg 2001; 95: 1-8.
49. Brown ES, Khan DA, Nejtek VA. The psychiatric side effects of corticosteroids. Ann Allergy Asthma Immunol 1999; 83: 495-503, quiz 503-494.
50. Sirois F. Steroid psychosis: a review. Gen Hosp Psychiatry 2003; 25: 27-33.
51. Sharfstein SS, Sack DS, Fauci AS. Relationship between alternate-day corticosteroid therapy and behavioral abnormalities. JAMA 1982; 248: 2987-2989.
52. Plotsky PM, Owens MJ, Nemeroff CB. Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am 1998; 21: 293-307.
53. Lopez JF, Little KY, Lopez-Figueroa AL, Lopez-Figueroa MO, Watson SJ In: Charney DS (ed) Society of Biological Psychiatry Annual Meeting, Vol 9s Elsevier Science Inc.: San Francisco, 2003.
54. Webster MJ, Knable MB, O'Grady J, Orthmann J, Weickert CS. Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Mol Psychiatry 2002; 7: 985-994, 924.
55. Nemeroff CB, Owens MJ, Bissette G, Andorn AC, Stanley M. Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988; 45: 577-579.
56. Young EA, Lopez JF, Murphy-Weinberg V, Watson SJ, Akil H. Mineralocorticoid receptor function in major depression. Arch Gen Psychiatry 2003; 60: 24-28.
57. Gould TD, Gray NA, Manji HK. The cellular neurobiology of severe mood and anxiety disorders: implications for the development of novel therapeutics. In: DS Charney (ed) Molecular Neurobiology for the Clinician. American Psychiatric Press, Inc.: Washington, 2003 pp 123-227.
58. Gold PW, Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 2002; 7: 254-275.
59. Wolkowitz OM, Reus VI, Chan T, Manfredi F, Raum W, Johnson R et al. Antiglucocorticoid treatment of depression: double-blind ketoconazole. Biol Psychiatry 1999; 45: 1070-1074.
60. Malison RT, Anand A, Pelton GH, Kirwin P, Carpenter L, McDougle CJ et al. Limited efficacy of ketoconazole in treatment-refractory major depression. J Clin Psychopharmacol 1999; 19: 466-470.
61. Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF. Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol 2001; 21: 516-521.
62. Young AH, Gallagher P, Watson S, Del-Estal D, Owen BM, Ferrier NI. Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Neuropsychopharmacology, (in press).
63. DeBattista C, Posener JA, Kalehzan BM, Schatzberg AF. Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study. Am J Psychiatry 2000; 157: 1334-1337.
64. Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L et al. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 1999; 156: 646-649.
65. Bloch M, Schmidt P, Danaceau MLA, Rubinow D. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry 1999; 45: 1533-1541.
66. Saunders J, Williams J. Antagonists of the corticotropin releasing factor receptor. Prog Med Chem 2003; 41: 195-247.
67. Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G. Neuropeptide system as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci 2003; 24: 580-588.
68. Webster EL, Lewis DB, Torpy DJ, Zachman EK, Rice KC, Chrousos GP. In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin- releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation. Endocrinology 1996; 137: 5747-5750.
69. Habib KE, Weld KP, Rice KC, Pushkas J, Champoux M, Listwak S et al. Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine and autonomic responses to stress in primates. Proc Natl Acad Sci USA 2000; 97: 6079-6084.
70. Ducottet C, Griebel G, Belzung C. Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 625-631.
71. Seymour PA, Schmidt AW, Schulz DW. The pharmacology of CP-154,526, a non-peptide antagonist of the CRH1 receptor: a review. CNS Drug Rev 2003; 9: 57-96.
72. Mansbach RS, Brooks EN, Chen YL. Antidepressant-like effects of CP-154,526, a selective CRF1 receptor antagonist. Eur J Pharmacol 1997; 323: 21-26.
73. Griebel G, Simiand J, Steinberg R, Jung M, Gully D, Roger P et al. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4- methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factorl receptor antagonist. II. Characterization in rodent models of stress-related disorders. J Pharmacol Exp Ther 2002; 301: 333-345.
74. Okuyama S, Chaki S, Kawashima N, Suzuki Y, Ogawa S, Nakazato A et al. Receptor binding, behavioral, and electrophysiological profiles of nonpeptide corticotropin-releasing factor subtype 1 receptor antagonists CRA1000 and CRA1001. J Pharmacol Exp Ther 1999; 289: 926-935.
75. Harro J, Tonissaar M, Eller M. The effects of CRA 1000, a nonpeptide antagonist of corticotropin-releasing factor receptor type 1, on adaptive behaviour in therat. Neuropeptides 2001; 35: 100-109.
76. Li, Y-W, Hill G, Wong H, Kelly N, Ward K, Pierdomenico M et al. Receptor occupancy of nonpeptide corticotropin-releasing factor 1 antagonist DMP696: correlation with drug exposure and anxiolytic efficacy. J Pharmacol Exp Ther 2003; 305: 86-96.
77. Zobel AW, Nickel T, Kunzel HE, Ackl N, Sonntag A, Ising M et al. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res 2000; 34: 171-181.
78. Kunzel HE, Zobel AW, Nickel T, Ackl N, Uhr M, Sonntag A et al. Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects. J Psychiatri Res 2003; 37: 525-533.
79. McEwen BS. Interacting mediators of allostasis and allostatic load: towards an understanding of resilience in aging. Metabolism 2003; 52: 10-16.
80. Wolkowitz OM, Reus VI, Roberts E, Manfredi F, Chan T, Raum WJ et al. Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry 1997; 41: 311-318.
81. Murphy BE, Filipini D, Ghadirian AM. Possible use of glucocorticoid receptor antagonists in the treatment of major depression: preliminary results using RU 486. J Psychiatry Neurosci 1993; 18: 209-213.
82. Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C et al. An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry 2002; 52: 386-392.
83. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, Gray NA et al. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 2003; 53: 707-742.
84. Young AH, Watson S, Gallagher P, Smith MS, Del-Estal D, Owen BM et al. Mifepristone (RU-486) in the treatment of bipolar disorder and schizophrenia. Biol Psychiatry 2003; 53: 406.
85. DeBattista C. C-1073 (Mifepristone) vs. placebo add-on to treatment as usual in patients with psychotic major depression. In: Difficult to Treat Mood and Anxiety Disorders. Washington DC, October 2003.
86. Bachmann CG, Linthorst AC, Holsboer F, Reul JM. Effect of chronic administration of selective glucocorticoid receptor antagonists on the rat hypothalamic-pituitary-adrenocortical axis. Neuropsychopharmacology 2003; 28: 1056-1067.
87. Hoyberg OJ, Wik G, Mehtonen OP, Peeters BWMM, Sennef C. ORG 34517, a selective glucocorticoid receptor antagonist with potent antidepressant activity: first clinical results. Int J Neuropsychopharmacol 2002; 5: 148.
88. Miner JN, Tyree C, Hu J, Berger E, Marschke K, Nakane M et al. A nonsteroidal glucocorticoid receptor antagonist. Mol Endocrinol 2003; 17: 117-127.
89. Honer C, Nam K, Fink C, Marshall P, Ksander G, Chatelain RE et al. Glucocorticoid receptor antagonism by cyproterone acetate and RU486. Mol Pharmacol 2003; 63: 1012-1020.
90. Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RG. Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature 1995; 378: 182-186.
91. Collingridge GL. Long-term potentiation. A question of reliability. Nature 1994; 371: 652-653.
92. Collingridge GL, Bliss TV. Memories of NMDA receptors and LTP. Trends Neurosci 1995; 18: 54-56.
93. Watkins J, Collingridge G. Phenylglycine derivatives as antagonists of metabotropic glutamate receptors. Trends Pharmacol Sci 1994; 15: 333-342.
94. Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 1989; 244: 798-800.
95. Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry 2000; 48: 755-765.
96. Patel M, Li QY. Age dependence of seizure-induced oxidative stress. Neuroscience 2003; 118: 431-437.
97. 2+ elevation in cultured rat hippocampal neurons. J Neurochem 2002; 83: 1441-1451.
98. Nair SM, Werkman TR, Craig J, Finnell R, Joels M, Eberwine JH. Corticosteroid regulation of ion channel conductances and mRNA levels in individual hippocampal CA1 neurons. J Neurosci 1998; 18: 2685-2696.
99. Weiland NG, Orchinik M, Tanapat P. Chronic corticosterone treatment induces parallel changes in N-methyl-D-aspartate receptor subunit messenger RNA levels and antagonist binding sites in the hippocampus. Neuroscience 1997; 78: 653-662.
100. Scaccianoce S, Matrisciano F, Del Bianco P, Caricasole A, Di Giorgi Gerevini V, Cappuccio I et al. Endogenous activation of group-II metabotropic glutamate receptors inhibits the hypothalamic-pituitary-adrenocortical axis. Neuropharmacology 2003; 44: 555-561.
101. Hergovich N, Singer E, Agneter E, Eichler HG, Graselli U, Simhandl C et al. Comparison of the effects of ketamine and memantine on prolactin and cortisol release in men. a randomized, double-blind, placebo-controlled trial. Neuropsychopharmacology 2001; 24: 590-593.
102. Zarate CA, Quiroz J, Payne J, Manji HK. Modulators of the glutamatergic system: implications for the development of improved therapeutics in mood disorders. Psychopharmacol Bull 2002; 36: 35-83.
103. Calabrese JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 1999; 60: 79-88.
104. Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA et al. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol 2000; 20: 607-614.
105. Bowden CL, Calabrese JR, Sachs G, Yatham LN, Asghar SA, Hompland M et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003; 60: 392-400.
106. Leach MJ, Marden CM, Miller AA. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia 1986; 27: 490-497.
107. Calabresi P, Siniscalchi A, Pisani A, Stefani A, Mercuri NB, Bernardi G. A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate in neocortical slices. Neurology 1996; 47: 557-562.
108. Wang SJ, Huang CC, Hsu KS, Tsai JJ, Gean PW. Presynaptic inhibition of excitatory neurotransmission by lamotrigine in the rat amygdalar neurons. Synapse 1996; 24: 248-255.
109. Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A et al. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Arch Gen Psychiatry 2000; 57: 270-276.
110. Benavides J, Camelin JC, Mitrani N, Flamand F, Uzan A, Legrand JJ et al. 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission-II. Biochemical properties. Neuropharmacology 1985; 24: 1085-1092.
111. Kretschmer BD, Kratzer U, Schmidt WJ. Riluzole, a glutamate release inhibitor, and motor behavior. Naunyn Schmiedebergs Arch Pharmacol 1998; 358: 181-190.
112. Doble A. The pharmacology and mechanism of action of riluzole. Neurology 1996; 47: S233-241.
113. Debono MW, Le Guern J, Canton T, Doble A, Pradier L. Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes. Eur J Pharmacol 1993; 235: 283-289.
114. Urbani A, Belluzzi O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci 2000; 12: 3567-3574.
115. Benoit E, Escande D. Riluzole specifically blocks inactivated Na channels in myelinated nerve fibre. Pflugers Arch 1991; 419: 603-609.
116. Cheramy A, Barbeito L, Godeheu G, Glowinski J. Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo. Neurosci Lett 1992; 147: 209-212.
117. Martin D, Thompson MA, Nadler JV. The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1. Eur J Pharmacol 1993; 250: 473-476.
118. Siniscalchi A, Bonci A, Mercuri NB, Bernardi G. Effects of riluzole on rat cortical neurones: an in vitro electrophysiological study. Br J Pharmacol 1997; 120: 225-230.
119. De Sarro G, Siniscalchi A, Ferreri G, Gallelli L, De Sarro A. NMDA and AMPA/kainate receptors are involved in the anticonvulsant activity of riluzole in DBA/2 mice. Eur J Pharmacol 2000; 408: 25-34.
120. Hubert JP, Burgevin MC, Terro F, Hugon J, Doble A. Effects of depolarizing stimuli on calcium homeostasis in cultured rat motoneurones. Br J Pharmacol 1998; 125: 1421-1428.
121. Keita H, Lepouse C, Henzel D, Desmonts JM, Mantz J. Riluzole blocks dopamine release evoked by N-methyl-D-aspartate, kainate, and veratridine in the rat striatum. Anesthesiology 1997; 87: 1164-1171.
122. Mizuta I, Ohta M, Ohta K, Nishimura M, Mizuta E, Kuno S. Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis in cultured mouse astrocytes. Neurosci Lett 2001; 310: 117-120.
123. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 2002; 22: 3251-3261.
124. Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH. Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major depressive disorder. Psychopharmacology 2003; 167: 219-220.
125. Singh J, Zarate CA, Krystal AD. Successful riluzole augmentation therapy in treatment-resistant bipolar depression following the development of rush with lamotrigine. Psychopharmacology 2004 (in press).
126. Zarate CAJ, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D et al. An open-label trial of riluzole in treatment-resistant major depression. Am J Psychiatry 2004; 161: 171-174.
127. Li X, Tizzano JP, Griffey K, Clay M, Lindstrom T, Skolnick P. Antidepressant-like actions of an AMPA receptor potentiator (LY392098). Neuropharmacology 2001; 40: 1028-1033.
128. Reynolds IJ, Miller RJ. Tricyclic antidepressants block N-methyl-D-aspartate receptors: similarities to the action of zinc. Br J Pharmacol 1988; 95: 95-102.
129. Trullas R, Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 1990; 185: 1-10.
130. Paul IA, Trullas R, Skolnick P, Nowak G. Down-regulation of cortical beta-adrenoceptors by chronic treatment with functional NMDA antagonists. Psychopharmacology (Berl) 1992; 106: 285-287.
131. Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry 1996; 29: 23-26.
132. Papp M, Moryl E, Maccecchini ML. Differential effects of agents acting at various sites of the NMDA receptor complex in a place preference conditioning model. Eur J Pharmacol 1996; 317: 191-196.
133. Cameron HA, McEwen BS, Gould E. Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci 1995; 15: 4687-4692.
134. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000; 47: 351-354.
135. Heresco-Levy U, Javitt DC. The role of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in the pathophysiology and therapeutics of psychiatric syndromes. Eur Neuropsychopharmacol 1998; 8: 141-152.
136. Crane G. The psychotropic effect of cycloserine: a new use of an antibiotic. Compr Psychiatry 1961; 2: 51-59.
137. Crane G. Cycloserine as an antidepressant agent. Am J Psychiatry 1959; 115: 1025-1026.
138. Vamvakides A. D-cycloserine is active in the adult mouse and inactive in the aged mouse, in the forced swim test. Ann Pharm Fr 1998; 56: 209-212.
139. Kornhuber J, Bormann J, Hubers M, Rusche K, Riederer P. Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. Eur J Pharmacol 1991; 206: 297-300.
140. Kornhuber J, Weller M, Schoppmeyer K, Riederer P. Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 1994; 43: 91-104.
141. Parsons CG, Quack G, Bresink I, Baran L, Przegalinski E, Kostowski W et al. Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo. Neuropharmacology 1995; 34: 1239-1258.
142. Parkes JD, Calver DM, Zilkha KJ, Knill-Jones RP. Controlled trial of amantadine hydrochloride in Parkinson's disease. Lancet 1970; 1: 259-262.
143. Vale S, Espejel MA, Dominguez JC. Amantadine in depression. Lancet 1971; 2: 437.
144. Rizzo M, Morselli PL. Amantadine-induced aggressiveness. BMJ 1972; 3: 50.
145. Areosa SA, Sherriff F. Memantine for dementia. Cochrane Database Syst Rev 2003 CD003154.
146. Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke 2002; 33: 1834-1839.
147. Reisberg B, Doody R, Stoffer A, Schmitt F, Ferris S, Mobius HJ. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003; 348: 1333-1341.
148. Bormann J. Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. Eur J Pharmacol 1989; 166: 591-592.
149. 3H]MK-801 binding to human hippocampal NMDA receptors. Neuroreport 1994; 5: 1237-1240.
150. Chen HS, Wang YF, Rayudu PV, Edgecomb P, Neill JC, Segal MM et al. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience 1998; 86: 1121-1132.
151. Chen HS, Lipton SA. Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism. J Physiol 1997; 499(Part 1): 27-46.
152. Moryl E, Danysz W, Quack G. Potential antidepressive properties of amantadine memantine and bifemelane. Pharmacol Toxicol 1993; 72: 394-397.
153. Rogoz Z, Skuza G, Maj J, Danysz W. Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 2002; 42: 1024-1030.
154. Ametamey SM, Samnick S, Leenders KL, Vontobel P, Quack G, Parsons CG et al. Fluorine-18 radiolabelling, biodistribution studies and preliminary PET evaluation of a new memantine derivative for imaging the NMDA receptor. J Recept Signal Transduct Res 1999; 19: 129-141.
155. 3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 1989; 166: 589-590.
156. Brown WM, Aiken SP. Felbamate: clinical and molecular aspects of a unique antiepileptic drug. Crit Rev Neurobiol 1998; 12: 205-222.
157. Wallis RA, Panizzon KL. Felbamate neuroprotection against CA1 traumatic neuronal injury. Eur J Pharmacol 1995; 294: 475-482.
158. Wallis RA, Panizzon KL, Fairchild MD, Wasterlain CG. Protective effects of felbamate against hypoxia in the rat hippocampal slice. Stroke 1992; 23: 547-551.
159. Ketter TA, Malow BA, Flamini R, Ko D, White SR, Post RM et al. Felbamate monotherapy has stimulant-like effects in patients with epilepsy. Epilepsy Res 1996; 23: 129-137.
160. Ketter TA, Post RM, Theodore WH. Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. Neurology 1999; 53: S53-67.
161. Gay PE, Mecham GF, Coskey JS, Sadler T, Thompson JA. Behavioral effects of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). Psychol Rep 1995; 77: 1208-1210.
162. 3H]glycine binding in rat brain and sections of human postmortem brain. J Pharmacol Exp Ther 1998; 286: 991-999.
163. Wamsley JK, Sofia RD, Faull RL, Narang N, Ary T, Gan XD et al. Felbamate: interaction with glycine receptors in human cerebral cortex. Proc West Pharmacol Soc 1994; 37: 81-83.
164. Coffin V, Cohen-Williams M, Barnett A. Selective antagonism of the anticonvulsant effects of felbamate by glycine. Eur J Pharmacol 1994; 256: R9-10.
165. Subramaniam S, Rho JM, Penix L, Donevan SD, Fielding RP, Rogawski MA. Felbamate block of the N-methyl-D-aspartate receptor. J Pharmacol Exp Ther 1995; 273: 878-886.
166. Kaufman DW, Kelly JP, Anderson T, Harmon DC, Shapiro S. Evaluation of case reports of aplastic anemia among patients treated with felbamate. Epilepsia 1997; 38: 1265-1269.
167. 2+: an endogenous modulator of ligand- and voltage-gated ion channels. Neuropharmacology 1994; 33: 935-952.
168. Nowak G, Schlegel-Zawadzka M. Alterations in serum and brain trace element levels after antidepressant treatment: part I. Zinc. Biol Trace Elem Res 1999; 67: 85-92.
169. Kroczka B, Branski P, Palucha A, Pilc A, Nowak G. Antidepressant-like properties of zinc in rodent forced swim test. Brain Res Bull 2001; 55: 297-300.
170. Szewczyk B, Branski P, Wieronska JM, Palucha A, Pilc A, Nowak G. Interaction of zinc with antidepressants in the forced swimming test in mice. Pol J Pharmacol 2002; 54: 681-685.
171. Nowak G, Szewczyk B, Wieronska JM, Branski P, Palucha A, Pilc A et al. Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats. Brain Res Bull 2003; 61: 159-164.
172. McLoughlin IJ, Hodge JS. Zinc in depressive disorder. Acta Psychiatr Scand 1990; 82: 451-453.
173. Maes M, Vandoolaeghe E, Neels H, Demedts P, Wauters A, Meltzer HY et al. Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biol Psychiatry 1997; 42: 349-358.
174. Nowak G, Siwek M, Dudek D, Zieba A, Pilc A. Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol 2003; 55: 1143-1147.
175. Ilouz R, Kaidanovich O, Gurwitz D, Eldar-Finkelman H. Inhibition of glycogen synthase kinase-3beta by bivalent zinc ions: insight into the insulin-mimetic action of zinc. Biochem Biophys Res Commun 2002; 295: 102-106.
176. Borges K, Dingledine R. AMPA receptors: molecular and functional diversity. Prog Brain Res 1998; 116: 153-170.
177. Bleakman D, Lodge D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 1998; 37: 1187-1204.
178. Goff DC, Leahy L, Berman I, Posever T, Herz L, Leon AC et al. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol 2001; 21: 484-487.
179. Knapp RJ, Goldenberg R, Shuck C, Cecil A, Watkins J, Miller C et al. Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model. Eur J Pharmacol 2002; 440: 27-35.
180. Skolnick P, Legutko B, Li X, Bymaster FP. Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res 2001; 43: 411-423.
181. Lauterborn JC, Lynch G, Vanderklish P, Arai A, Gall CM. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci 2000; 20: 8-21.
182. Bai F, Bergeron M, Nelson DL. Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus. Neuropharmacology 2003; 44: 1013-1021.
183. Anwyl R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 1999; 29: 83-120.
184. + current by a protein kinase-mediated mechanism. Neurosci Lett 1990; 112: 76-81.
185. Ikeda SR, Lovinger DM, McCool BA, Lewis DL. Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: subtype-specific coupling to ion channels. Neuron 1995; 14: 1029-1038.
186. Salinska E, Stafiej A. Metabotropic glutamate receptors (mGluRs) are involved in early phase of memory formation: possible role of modulation of glutamate release. Neurochem Int 2003; 43: 469-474.
187. Tan Y, Hori N, Carpenter DO. The mechanism of presynaptic long-term depression mediated by group I metabotropic glutamate receptors. Cell Mol Neurobiol 2003; 23: 187-203.
188. Riedel G, Platt B, Micheau J. Glutamate receptor function in learning and memory. Behav Brain Res 2003; 140: 1-47.
189. Nicoletti F, Bruno V, Copani A, Casabona G, Knopfel T. Metabotropic glutamate receptors: a new target for the therapy of neurodegenerative disorders? Trends Neurosci 1996; 19: 267-271.
190. Schoepp DD. Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 2001; 299: 12-20.
191. Maiese K, Vincent A, Lin SH, Shaw T. Group I and group III metabotropic glutamate receptor subtypes provide enhanced neuroprotection. J Neurosci Res 2000; 62: 257-272.
192. Spooren WP, Vassout A, Neijt HC, Kuhn R, Gasparini F, Roux S et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)-pyridine in rodents. J Pharmacol Exp Ther 2000; 295: 1267-1275.
193. Tatarczynska E, Klodzinska A, Chojnacka-Wojcik E, Palucha A, Gasparini F, Kuhn R et al. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 2001; 132: 1423-1430.
194. Tatarczynska E, Klodzinska A, Kroczka B, Chojnacka-Wojcik E, Pilc A. The antianxiety-like effects of antagonists of group I and agonists of group II and III metabotropic glutamate receptors after intrahippocampal administration. Psychopharmacology (Berl) 2001; 158: 94-99.
195. Chojnacka-Wojcik E, Klodzinska A, Pilc A. Glutamate receptor ligands as anxiolytics. Curr Opin Invest Drugs 2001; 2: 1112-1119.
196. Duman RS. Synaptic plasticity and mood disorders. Mol Psychiatry 2002; 7(Suppl 1): S29-S34.
197. Takahashi M, Terwilliger R, Lane C, Mezes PS, Conti M, Duman RS. Chronic antidepressant administration increases the expression of cAMP-specific phosphodiesterase 4A and 4B isoforms. J Neurosci 1999; 19: 610-618.
198. Nibuya M, Nestler EJ, Duman RS. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996; 16: 2365-2372.
199. Asanuma M, Nishibayashi S, Iwata E, Kondo Y, Nakanishi T, Vargas MG et al. Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor. Brain Res Mol Brain Res 1996; 41: 210-215.
200. Fujimaki K, Morinobu S, Duman RS. Administration of a cAMP phosphodiesterase 4 inhibitor enhances antidepressant-induction of BDNF mRNA in rat hippocampus. Neuropsychopharmacology 2000; 22: 42-51.
201. O'Donnell JM. Antidepressant-like effects of rolipram and other inhibitors of cyclic adenosine monophosphate phosphodiesterase on behavior maintained by differential reinforcement of low response rate. J Pharmacol Exp Ther 1993; 264: 1168-1178.
202. Griebel G, Misslin R, Vogel E, Bourguignon JJ. Behavioral effects of rolipram and structurally related compounds in mice: behavioral sedation of cAMP phosphodiesterase inhibitors. Pharmacol Biochem Behav 1991; 39: 321-323.
203. Wachtel H, Schneider HH. Rolipram, a novel antidepressant drug, reverses the hypothermia and hypokinesia of monoamine-depleted mice by an action beyond postsynaptic monoamine receptors. Neuropharmacology 1986; 25: 1119-1126.
204. Zeller E, Stief HJ, Pflug B, Sastre-y-Hernandez M. Results of a phase II study of the antidepressant effect of rolipram. Pharmacopsychiatry 1984; 17: 188-190.
205. Bobon D, Breulet M, Gerard-Vandenhove MA, Guiot-Goffioul F, Plomteux G, Sastre-y-Hernandez M et al. Is phosphodiesterase inhibition a new mechanism of antidepressant action? A double blind double-dummy study between rolipram and desipramine in hospitalized major and/or endogenous depressives. Eur Arch Psychiatry Neurol Sci 1988; 238: 2-6.
206. Fleischhacker WW, Hinterhuber H, Bauer H, Pflug B, Berner P, Simhandl C et al. A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. Neuropsychobiology 1992; 26: 59-64.
207. Hebenstreit GF, Fellerer K, Fichte K, Fischer G, Geyer N, Meya U et al. Rolipram in major depressive disorder: results of a double-blind comparative study with imipramine. Pharmacopsychiatry 1989; 22: 156-160.
208. Bertolino A, Crippa D, di Dio S, Fichte K, Musmeci G, Porro V et al. Rolipram versus imipramine in inpatients with major, 'minor' or atypical depressive disorder: a double-blind double-dummy study aimed at testing a novel therapeutic approach. Int Clin Psychopharmacol 1988; 3: 245-253.
209. Horowski R, Sastre-Y-Hernandez M. Clinical effects of the neurotropic selective cAMP phosphodiesterase inhibitor rolipram in depressed patients: global evaluation of the preliminary reports. Curr Ther Res 1985; 38: 23-29.
210. Scott AI, Perini AF, Shering PA, Whalley LJ. In-patient major depression: is rolipram as effective as amitriptyline? Eur J Clin Pharmacol 1991; 40: 127-129.
211. Huang Z, Ducharme Y, Macdonald D, Robichaud A. The next generation of PDE4 inhibitors. Curr Opin Chem Biol 2001; 5: 432-438.
212. Dyke HJ, Montana JG. Update on the therapeutic potential of PDE4 inhibitors. Expert Opin Invest Drugs 2002; 11: 1-13.
213. Ochs G, Penn RD, York M, Giess R, Beck M, Tonn J et al. A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1: 201-206.
214. Chen DF, Tonegawa S. Why do mature CNS neurons of mammals fail to re-establish connections following injury - functions of bcl-2. Cell Death Differ 1998; 5: 816-822.
215. Chen DF, Schneider GE, Martinou JC, Tonegawa S. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 1997; 385: 434-439.
216. Holm KH, Cicchetti F, Bjorklund L, Boonman Z, Tandon P, Costantini LC et al. Enhanced axonal growth from fetal human bcl-2 transgenic mouse dopamine neurons transplanted to the adult rat striatum. Neuroscience 2001; 104: 397-405.
217. Oh YJ, Swarzenski BC, O'Malley KL. Overexpression of Bcl-2 in a murine dopaminergic neuronal cell line leads to neurite outgrowth. Neurosci Lett 1996; 202: 161-164.
218. Chierzi S, Strettoi E, Cenni MC, Maffei L. Optic nerve crush: axonal responses in wild-type and bcl-2 transgenic mice. J Neurosci 1999; 19: 8367-8376.
219. DeVries AC, Joh HD, Bernard O, Hattori K, Hurn PD, Traystman RJ et al. Social stress exacerbates stroke outcome by suppressing Bcl-2 expression. Proc Natl Acad Sci USA 2001; 98: 11824-11828.
220. Takata K, Kitamura Y, Kakimura J, Kohno Y, Taniguchi T. Increase of bcl-2 protein in neuronal dendritic processes of cerebral cortex and hippocampus by the antiparkinsonian drugs, talipexole and pramipexole. Brain Res 2000; 236-241.
221. Zarate Jr CA, Payne JL, Singh J, Quiroz J, Luckenbaugh, Denicoff KD et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psych 2004 (in press).
222. Goldberg JF, Burdick KE, Endick CJ. A preliminary randomized, double-blind, placebo-controlled trial of primapexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004; 161: 564-566.
223. Manji HK, Gottesman II, Gould TD. Signal transduction and genes-to-behaviors pathways in psychiatric diseases. Sci STKE 2003; 207, pe49.
224. Einat H, Belmaker RH, Manji HK. New aproaches to modeling bipolar disorder. Psychopharm Bul 2003; 37: 47-63.
225. Nestler EJ, Gould E, Manji HK, Buncan M, Duman RS, Greshenfeld HK et al. Preclinical models: status of basic research in depression. Biol Psychiatry 2002; 52: 503-528.
226. Potter WZ, Ozcan ME. Methodological considerations for the development of new treatments for bipolar disorder. Aust NZJ Psychiatry 1999; 33(Suppl): S84-98.
227. Manji HK, Zarate CA. Molecular and cellular mechanisms underlying mood stabilization in bipolar disorder: implications for the development of improved therapeutics. Mol Psychiatry 2002; 7(Suppl 1): S1-S7.
228. Charney DS, Manji HK. Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for intervention. Sci STKE. 2004; RE5.
229. Danysz W, Parsons CG, Kornhuber J, Schmidt WJ, Quack G. Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents-preclinical studies. Neurosci Biobehav Rev 1997; 21: 455-468.
230. Parsons CG, Panchenko VA, Pinchenko VO, Tsyndrenko AY, Krishtal OA. Comparative patch-clamp studies with freshly dissociated rat hippocampal and striatal neurons on the NMDA receptor antagonistic effects of amantadine and memantine. Eur J Neurosci 1996; 8: 446-454.
231. Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L et al. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 2003; 23: 7311-7316.
232. Murphy BE. Treatment of major depression with steroid suppressive drugs. J Steroid Biochem Mol Biol 1991; 39: 239-244.
233. Ghadirian AM, Engelsmann F, Dhar V, Filipini D, Keller R, Chouinard G et al. The psychotropic effects of inhibitors of steroid biosynthesis in depressed patients refractory to treatment. Biol Psychiatry 1995; 37: 369-375.
234. Wolkowitz OM, Reus VI, Manfredi F, Ingbar J, Brizendine L, Weingartner H. Ketoconazole administration in hypercortisolemic depression. Am J Psychiatry 1993; 150: 810-812.
235. O'Dwyer AM, Lightman SL, Marks MN, Checkley SA. Treatment of major depression with metyrapone and hydrocortisone. J Affect Disord 1995; 33: 123-128.
236. Thakore JH, Dinan TG. Cortisol synthesis inhibition: a new treatment strategy for the clinical and endocrine manifestations of depression. Biol Psychiatry 1995; 37: 364-368.
237. Iizuka H, Kishimoto A, Nakamura J, Mizukawa R. Clinical effects of cortisol synthesis inhibition on treatment-resistant depression. Nihon Shinkei Seishin Yakurigaku Zasshi 1996; 16: 33-36.
238. Raven PW, O'Dwyer AM, Taylor NF, Checkley SA. The relationship between the effects of metyrapone treatment on depressed mood and urinary steroid profiles. Psychoneuroendocrinology 1996; 21: 277-286.
239. Sovner R, Fogelman S. Ketoconazole therapy for atypical depression. J Clin Psychiatry 1996; 57: 227-228.
240. Brown ES, Bobadilla L, Rush AJ. Ketoconazole in bipolar patients with depressive symptoms: a case series and literature review. Bipolar Disord 2001; 3: 23-29.
241. Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, Heckers S. Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychitary 2004; 61: 300-308.
242. Kato T, Kato N. Mitochondrial dysfunction in bipolar disoder. Bipolar Disord 2000; 2: 180-190.
243. Modica-Napolitano JS, Renshaw PF. Ethanolamine phosphoethanolamine inhibit mitochondrial function in vitro: implications for mitochondrial dysfunction hypothesis in depression and bipolar disorder. Biol Psychiatry 2004; 55: 273-277.
244. Gray NA, Quiroz JA, Kato T, Manji HK. Critical roles for the mitochondrial-ER network in the pathophysiology and treatement of bipolar disorder. 2004 Submitted.
245. Baker SK, Tarnopolsky MA. Targeting celluar energy production in neurological disorders. Expert Opin Invest Drugs 2003; 12: 1655-1679.
246. Pettegrew JW, Levine J, McClure RJ. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease geriatric depression. Mol Psychiarty 2000; 5: 616-632.