Antidepressant modulation of isolation and restraint stress effects on brain chemistry and morphology

B. S. McEwen, J. Angulo, E. Gould, S. Mendelson, Y. Watanabe

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Stress elicits adaptive responses from the brain, but it can also lead to maladaptive consequences. For example, stress can precipitate mental illness, including depression. Prolonged stress also causes damage to neurons in the hippocampus. Antidepressant drugs must be evaluated, not only for their ability to potentiate adaptive responses, but also to inhibit maladaptive consequences of stress. Ongoing research in our laboratory has compared the atypical tricyclic antidepressant, tianeptine, with the typical tricyclics, desipramine and imipramine, with respect to the effects of isolation and repeated restraint stress. Tianeptine and desipramine similarly attenuated isolation stress-induced increases in locus coeruleus and midbrain tyrosine hydroxylase mRNA levels and isolation-stress induced decreases in preproenkephalin mRNA levels in striatum and nucleus accumbens. However, tianeptine and imipramine differed in their effects in the cerebral cortex and hippocampus on 5HT2 and 5HT(1A) receptor levels but, surprisingly, produced similar effects on levels of the serotonin transporter labelled with [3H] paroxetine. Tianeptine also prevented stress-induced reductions in the length and number of branchpoints of dendrites of CA3 pyramidal neurons in hippocampus; comparison with effects of typical tricyclics are ongoing. Tianeptine also blocked effects of corticosterone treatment to reduce branching and length of CA3 dendrites. These actions of tianeptine may be due to interactions between 5HT and excitatory amino acids in the mossy fiber terminals on CA3 pyramidal neurons. Taken together, these results indicate that tianeptine has unique properties compared to some other antidepressant drugs, but shares in common with those drugs the ability to attenuate stress effects on tyrosine hydroxylase gene expression and on the serotonin transporter. It remains to be seen whether these actions are the basis of a common antidepressant action.

Original languageEnglish (US)
Pages (from-to)41s-48s
JournalEuropean Psychiatry
Issue numberSUPPL. 2
StatePublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health


  • antidepressant
  • desipramine
  • hippocampus
  • imipramine
  • serotonin
  • stress
  • tianeptine
  • tyrosine hydroxylase


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