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ARTICLE, Cellular/Molecular

Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus

Jessica E. Malberg, Amelia J. Eisch, Eric J. Nestler and Ronald S. Duman
Journal of Neuroscience 15 December 2000, 20 (24) 9104-9110; https://doi.org/10.1523/JNEUROSCI.20-24-09104.2000
Jessica E. Malberg
1Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut 06508
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Amelia J. Eisch
1Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut 06508
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Eric J. Nestler
1Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut 06508
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Ronald S. Duman
1Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut 06508
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Abstract

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.

  • proliferation
  • granule cell
  • fluoxetine
  • tranylcypromine
  • reboxetine
  • depression
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The Journal of Neuroscience: 20 (24)
Journal of Neuroscience
Vol. 20, Issue 24
15 Dec 2000
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Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus
Jessica E. Malberg, Amelia J. Eisch, Eric J. Nestler, Ronald S. Duman
Journal of Neuroscience 15 December 2000, 20 (24) 9104-9110; DOI: 10.1523/JNEUROSCI.20-24-09104.2000

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Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus
Jessica E. Malberg, Amelia J. Eisch, Eric J. Nestler, Ronald S. Duman
Journal of Neuroscience 15 December 2000, 20 (24) 9104-9110; DOI: 10.1523/JNEUROSCI.20-24-09104.2000
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Keywords

  • proliferation
  • granule cell
  • fluoxetine
  • tranylcypromine
  • reboxetine
  • depression

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