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Synaptic plasticity and mood disorders

Molecular Psychiatry volume 7, pages S29–S34 (2002)Cite this article

Abstract

Recent studies demonstrate that the molecular elements known to regulate neuronal plasticity in models of learning and memory are also involved in the actions of drugs used for the treatment of depression and bipolar disorder. This includes up-regulation of transcription factors, such as the cAMP response element binding protein and neurotrophic factors, such as brain derived neurotrophic factor. These findings raise the possibility that regulation of neural plasticity in specific neuronal circuits is integrally involved in the therapeutic intervention of mood disorders. Atypical antipsychotic drugs, including clozapine and olanzapine, are also effective for the treatment of bipolar disorder, and are used as add-on medication for unipolar depression. The possibility that these atypical antipsychotic drugs also influence the molecular determinants of synaptic plasticity that are involved in the response to drugs used for the treatment of mood disorders, is discussed.

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References

  1. Figurov A, Pozzo ML, Olafsson P, Wang T, Lu B . Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus Nature 1996 381: 706–709

    Article  CAS  Google Scholar 

  2. Silva A, Kogan JH, Frankland PW, Kida S . CREB and memory Ann Rev Neurosci 1998 21: 127–148

    Article  CAS  Google Scholar 

  3. Duman R, Heninger GR, Nestler EJ . A molecular and cellular theory of depression Arch Gen Psychiatry 1997 54: 597–606

    Article  CAS  Google Scholar 

  4. Duman R, Malberg J, Nakagawa S, D'Sa C . Neuronal plasticity and survival in mood disorders Biol Psychiatry 2000 48: 732–739

    Article  CAS  Google Scholar 

  5. Manji H, Moore GJ, Chen G . Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness Biol Psychiatry 2000 48: 740–754

    Article  CAS  Google Scholar 

  6. Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E . Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory PNAS USA 1998 95: 15020–15025

    Article  CAS  Google Scholar 

  7. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME . Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms Science 1999 286: 1358–1362

    Article  CAS  Google Scholar 

  8. Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DD . Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons Science 1999 286: 2358–2361

    Article  CAS  Google Scholar 

  9. Finkbeiner S . CREB couples neurotrophin signals to survival messages Neuron 2000 25: 11–14

    Article  CAS  Google Scholar 

  10. 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

    Article  CAS  Google Scholar 

  11. Thome J, Sakai N, Shin K, Steffen C, Zhang YJ, Impey S et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment J Neurosci 2000 20: 4030–4036

    Article  CAS  Google Scholar 

  12. Thome J, Sakai N, Shin KH, Steffen C, Impey S, Storm DR et al. Regulation of cAMP-response-element promoter activity by antidepressant treatment in CRE-lacZ transgenic mice Soc Neurosci 1998 24: 1844

    Google Scholar 

  13. Konradi C, Heckers S . Haloperidol-induced fos expression in striatum is dependent upon transcription factor cyclic AMP response element binding protein Neuroscience 1995 65: 1051–1061

    Article  CAS  Google Scholar 

  14. Chen A-H, Shirayama Y, Shin KH, Neve RL, Duman RS . Expression of the cAMP response element binding protein (CREB) in hippocampus produces antidepressant effect Biol Psychiatry 2001 49: 753–762

    Article  CAS  Google Scholar 

  15. Dowlatshahi D, MacQueen GM, Wang JF, Young LT . Increased temporal cortex CREB concentrations and antidepressant treatment in major depression The Lancet 1998 352: 1754–1755

    Article  CAS  Google Scholar 

  16. Goldberg J, Barres BA . The relationship between neuronal survival and regeneration Ann Rev Neurosci 2000 23: 579–612

    Article  CAS  Google Scholar 

  17. McAllister K, Katz LC, Lo DC . Neurotrophins and synaptic plasticity Ann Rev Neurosci 1999 22: 295–318

    Article  CAS  Google Scholar 

  18. Nibuya M, Morinobu S, Duman RS . Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments J Neurosci 1995 15: 7539–7547

    Article  CAS  Google Scholar 

  19. Rosello-Neustadt ABR, Cotman CW . Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression Neuropsychopharmacology 1999 21: 679–682

    Article  Google Scholar 

  20. Angelucci F, Mathe AE, Aloe L . Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration J Neurosci Res 2000 60: 783–794

    Article  CAS  Google Scholar 

  21. Dawson N, Hamid EH, Egan MF, Meredith GE . Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment Synapse 2001 39: 70–81

    Article  CAS  Google Scholar 

  22. Linden A, Vaisanen J, Lakso M, Nawa H, Wong G, Castren E . Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain after administration of antipsychotic and psychotrophic agents J Mol Neurosci 2000 14: 27–37

    Article  CAS  Google Scholar 

  23. Ozaki T . Comparative effects of dopamine D(1) and D(2) receptor antagonists on nerve growth factor protein induction Eur J Pharmacol 2000 402: 39–44

    Article  CAS  Google Scholar 

  24. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay R . Antidepressant-like effect of brain derived neurotrophic factor (BDNF) Pharmacol Biochem Behav 1996 56: 131–137

    Article  Google Scholar 

  25. Mamounas L, Blue ME, Siuciak JA, Anthony AC . BDNF promotes the survival and sprouting of serotonergic axons in the rat brain J Neurosci 1995 15: 7929–7939

    Article  CAS  Google Scholar 

  26. Shirayama Y, Chen ACH, Duman RS . Antidepressant-like effects of BDNF and NT-3 in behavioral models of depression Soc Neurosci 2000 26: 1042

    Google Scholar 

  27. Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E . Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress PNAS USA 1998 95: 3168–3171

    Article  CAS  Google Scholar 

  28. McEwen B . Stress and hippocampal plasticity Curr Opin Neurobiol 1999 5: 205–216

    Article  Google Scholar 

  29. Sapolsky R . Stress, glucocorticoids, and damage to the nervous system: the current state of confusion Stress 1996 1: 1–19

    Article  CAS  Google Scholar 

  30. Smith MA, Makino S, Altemus M, Michelson D, Hong S-K, Kvetnansky R et al. Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus PNAS USA 1995 92: 8788–8792

    Article  CAS  Google Scholar 

  31. Bremner J, Narayan M, Anderson ER, Staib LH, Miller H, Charney DS . Smaller hippocampal volume in major depression Am J Psychiatry 2000 157: 115–117

    Article  CAS  Google Scholar 

  32. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder Am J Psychiatry 1995 152: 973–981

    Article  CAS  Google Scholar 

  33. Sheline Y, Wany P, Gado MH, Csernansky JG, Vannier MW . Hippocampal atrophy in recurrent major depression PNAS USA 1996 93: 3908–3913

    Article  CAS  Google Scholar 

  34. Drevets WC, Price JL, Simpson JR et al. Subgenual prefrontal cortex abnormalities in mood disorders Nature 1997 386: 824–827

    Article  CAS  Google Scholar 

  35. Ongur D, Drevets WC, Price JL . Glial reduction in the subgenual prefrontal cortex in mood disorders PNAS USA 1998 95: 13290–13295

    Article  CAS  Google Scholar 

  36. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression Biol Psychiatry 1999 45: 1085–1098

    Article  CAS  Google Scholar 

  37. Gage F . Mammalian neural stem cells Science 2000 287: 1433–1438

    Article  CAS  Google Scholar 

  38. Gould E, Tanapat P, Hastings NB, Shors TJ . Neurogenesis in adulthood: a possible role in learning Trends Cognit Sci 1999 3: 186–192

    Article  CAS  Google Scholar 

  39. Gould E, McEwen BS, Tanapat P, Galea LAM, Fuchs E . Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation J Neurosci 1997 17: 2492–2498

    Article  CAS  Google Scholar 

  40. Malberg J, Eisch AJ, Nestler EJ, Duman RS . Chronic antidepressant treatment increases neurogenesis in adult hippocampus J Neurosci 2000 20: 9104–9110

    Article  CAS  Google Scholar 

  41. Eisch A, Barrot M, Schad CA, Self DW, Nestler EJ . Opiates inhibit neurogenesis in the adult rat hippocampus PNAS USA 2000 97: 7579–7584

    Article  CAS  Google Scholar 

  42. Jacobs B, Fornal CA . Chronic fluoxetine treatment increases hippocampal neurogenesis in rats: a novel theory of depression Soc Neurosci Abstracts, Miami, FL 1999

    Google Scholar 

  43. Madsen T, Treschow A, Bengzon J, Bolwig TG, Lindvall O, Tingström . Increased neurogenesis in a model of electroconvulsive therapy Biol Psychiatry 2000 47: 1043–1049

    Article  CAS  Google Scholar 

  44. Manev H, Uz T, Smalheiser NR, Manev R . Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro Eur J Pharmacol 2000 411: 67–70

    Article  Google Scholar 

  45. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK . Enhancement of hippocampal neurogenesis by lithium J Neurochem 2000 75: 1729–1734

    Article  CAS  Google Scholar 

  46. Backhouse B, Barochovsky O, Malik C, Patel A, Lewis P . Effect of haloperidol on cell proliferation in the early postnatal rat brain Neuropathol Appl Neurobiol 1982 8: 109–116

    Article  CAS  Google Scholar 

  47. Dawirs R, Hildebrandt K, Teuchert-Noodt G . Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus J Neural Transm 1998 105: 317–327

    Article  CAS  Google Scholar 

  48. Kim J-E, Nakagawa S, Duman RS . Chronic administration of rolipram, a cAMP phosphodiesterase-4 inhibitor, upregulates neurogenesis in the adult mouse hippocampus Soc Neurosci Abs 2000 26: 2316

    Google Scholar 

  49. Nakagawa S, Kim J-E, Lee R, Chen J, Duman RS . CREB plays a critical role in the survival of newborn cells in the adult hippocampus Soc Neurosci 2000 Abstr 26 2317

  50. Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS . Tianeptine attenuates stress-induced morphological changes in the hippocampus Eur J Pharmacol 1992 222: 157–162

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work is supported by USPHS grants MH45481 and 2 PO1 MH25642, a Veterans Administration National Center Grant for PTSD.

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  1. Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA

    R S Duman

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  1. R S Duman
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Duman, R. Synaptic plasticity and mood disorders. Mol Psychiatry 7 (Suppl 1), S29–S34 (2002). https://doi.org/10.1038/sj.mp.4001016

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