Prenatal stress alters diazepam withdrawal syndrome and 5HT1A receptor expression in the raphe nuclei of adult rats

Neuroscience. 2016 Aug 25;330:50-6. doi: 10.1016/j.neuroscience.2016.05.035. Epub 2016 May 26.

Abstract

Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring. The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5mg/kg/day i.p for 1week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats.

Keywords: 5HT1A receptors; diazepam withdrawal; prenatal stress; raphe nuclei.

MeSH terms

  • Animals
  • Diazepam / adverse effects*
  • Diazepam / pharmacology
  • Electroshock
  • Female
  • GABA Modulators / adverse effects*
  • GABA Modulators / pharmacology
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • RNA, Messenger / metabolism
  • Random Allocation
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / growth & development
  • Raphe Nuclei / metabolism*
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Stress, Psychological* / physiopathology
  • Substance Withdrawal Syndrome / metabolism*

Substances

  • GABA Modulators
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT1A
  • Diazepam