Neural plasticity to stress and antidepressant treatment

Biol Psychiatry. 1999 Nov 1;46(9):1181-91. doi: 10.1016/s0006-3223(99)00177-8.


Adaptations at the cellular and molecular levels in response to stress and antidepressant treatment could represent a form of neural plasticity that contributes to the pathophysiology and treatment of depression. At the cellular level, atrophy and death of stress-vulnerable neurons in the hippocampus, as well as decreased neurogenesis of hippocampal neurons, has been reported in preclinical studies. Clinical studies also provide evidence for atrophy and cell death in the hippocampus, as well as the prefrontal cortex. It is possible that antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function. The molecular mechanisms underlying these effects are discussed, including the role of the cAMP signal transduction cascade and neurotrophic factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Cell Death
  • Corticotropin-Releasing Hormone / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Depression / drug therapy
  • Depression / metabolism
  • Depression / physiopathology*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Neuronal Plasticity / drug effects*
  • Norepinephrine / metabolism
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology
  • Signal Transduction / drug effects
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology*


  • Antidepressive Agents
  • Corticotropin-Releasing Hormone
  • Cyclic AMP-Dependent Protein Kinases
  • Norepinephrine