Sensitivity of hippocampal 5-HT1A receptors to mild stress in BDNF-deficient mice

Teresa F. Burke, Tushar Advani, Megumi Adachi, Lisa M. Monteggia, Julie G. Hensler

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Serotonin 1A (5-HT1A) receptors in brain play an important role in cognitive and integrative functions, as well as emotional states. Decreased brain-derived neurotrophic factor (BDNF) expression and/or function, particularly in hippocampus, are implicated in the pathophysiology of stress-related disorders such as major depression. BDNF+/- mice are more vulnerable to stress than wild-type mice, exhibiting behavioural despair after mild handling stress. We examined the effect of mild handling stress on 5-HT1A receptor function, as measured by 8-OH-DPAT stimulated [ 35S]GTPγS binding, in BDNF+/- mice and mice with a forebrain-specific reduction in BDNF (embryonic BDNF inducible knockout mice). Our data show a remarkable sensitivity of hippocampal 5-HT1A receptors to mild stress and a deficiency in BDNF. Other 5-HT1A receptor populations, specifically in frontal cortex and dorsal raphe, were resistant to the combined detrimental effects of mild stress and reductions in BDNF expression. Decreases in hippocampal 5-HT1A receptor function induced by mild stress in BDNF-deficient mice were prevented by administration of the selective serotonin reuptake inhibitor fluoxetine, which increased activation of TrkB, the high affinity receptor for BDNF, in wild-type and BDNF+/- mice. In hippocampal cultures, BDNF increased the capacity of 5-HT1A receptors to activate G proteins, an effect eliminated by the knockout of TrkB, confirming TrkB activation increases 5-HT1A receptor function. The mechanisms underlying the sensitivity of hippocampal 5-HT1A receptors to mild stress and decreased BDNF expression remain to be elucidated and may have important implications for the emotional and cognitive impairments associated with stress-related mental illness.

Original languageEnglish (US)
Pages (from-to)631-645
Number of pages15
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number3
DOIs
StatePublished - Apr 1 2013

Keywords

  • Antidepressant
  • frontal cortex
  • hippocampus
  • raphe
  • serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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