Effect of early rearing conditions on alcohol drinking and 5-HT 1A receptor function in C57BL/6J mice

Tushar Advani, Julie G. Hensler, Wouter Koek

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


We have evaluated in C57BL/6J mice the effect of maternal separation and post-weaning social isolation on ethanol intake, and on serotonin1A (5-HT 1A) receptor function at the level of receptor-G protein interaction in the hippocampus and dorsal raphe nucleus. From postnatal days 2-14, litters were separated from the mother for 15 min (Handled) or for 180 min (Maternal separation). After weaning, pups were housed in pairs or in social isolation. At 2 months of age, ethanol intake and preference in mice were assessed using the two-bottle choice paradigm. Maternal separation increased ethanol preference in female mice that were subsequently housed in isolation. By contrast, post-weaning isolation increased ethanol preference and consumption in male mice regardless of pre-weaning rearing conditions. The increased ethanol preference and intake were limited to a 5% (v/v) concentration of ethanol. Our data suggest that adolescent mice are susceptible to the effects of post-weaning social isolation as shown by increased ethanol preference and consumption. Using quantitative autoradiography, 5-HT1A receptor number and function were determined by the binding of [3H]WAY-100635, and by [ 35S]GTPγS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT, respectively. The binding experiments were done at approximately 3 months after the end of the two-bottle choice test in an attempt to minimize direct effects of ethanol drinking on 5-HT1A receptor function and number. 5-HT1A receptor-stimulated [35S] GTPγS binding in the dorsal raphe nucleus was increased in animals reared after weaning in isolation vs. in pairs, regardless of gender or pre-weaning rearing conditions. Our data suggest that there are long-term neurochemical consequences of social isolation of adolescent mice, specifically increased 5-HT1A receptor function in the dorsal raphe nucleus.

Original languageEnglish (US)
Pages (from-to)595-607
Number of pages13
JournalInternational Journal of Neuropsychopharmacology
Issue number5
StatePublished - 2007


  • 5-HT receptor
  • Alcohol
  • Maternal separation
  • Social isolation
  • [S]GTPγS binding

ASJC Scopus subject areas

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


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