The effects of chronic stress on hippocampal adult neurogenesis and dendritic plasticity are reversed by selective MAO-A inhibition

J Psychopharmacol. 2014 Dec;28(12):1178-83. doi: 10.1177/0269881114553646. Epub 2014 Oct 14.


There is accumulating evidence that adult neurogenesis and dendritic plasticity in the hippocampus are neuroplastic phenomena, highly sensitive to the effects of chronic stress and treatment with most classes of antidepressant drugs, being involved in the onset and recovery from depression. However, the effects of antidepressants that act through the selective inhibition of monoamine oxidase subtype A (MAO-A) in these phenomena are still largely unknown. In the present study, adult neurogenesis and neuronal morphology were examined in the hippocampus of rats exposed to chronic mild stress (CMS) and treated with the selective reversible MAO-A inhibitor (RIMA) drug, pirlindole and the selective serotonin reuptake inhibitor (SSRI), fluoxetine. The results provide the first demonstration that selective MAO-A inhibition with pirlindole is able to revert the behavioural effects of stress exposure while promoting hippocampal adult neurogenesis and rescuing the stress-induced dendritic atrophy of granule neurons.

Keywords: Depression; fluoxetine; hippocampus; neurogenesis; neuroplasticity; pirlindole; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy / pathology
  • Carbazoles / pharmacology*
  • Dendrites / drug effects*
  • Dendrites / pathology
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Male
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase / physiology*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Rats
  • Serotonin Uptake Inhibitors / pharmacology
  • Stress, Psychological / drug therapy
  • Stress, Psychological / pathology*
  • Stress, Psychological / physiopathology


  • Carbazoles
  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Monoamine Oxidase
  • pirlindole