Social Housing Conditions and Oxytocin and Vasopressin Receptors Contribute to Ethanol Conditioned Social Preference in Female Mice

Social behavior modulates response to alcohol. Because oxytocin (OXT) and vasopressin (AVP) contribute to rewarding social behavior, the present study utilized a genetic strategy to determine whether OXT and AVP receptors (OXTR, AVPR1a) are essential for female mice to demonstrate a conditioned social preference for ethanol. The study compared wild-type (WT) and knock-out (KO) females lacking either Oxtr or Avpr1a in a conditioned social preference (CSP) test. KO females and WT females from Het-Het crosses were pair-housed: KO and WT(ko). WT females from Het-WT crosses were pair-housed: WT(wt). Test mice received 2g/kg ethanol or saline ip, and were paired four times each with one stimulus female (CS-) after saline, and with another female (CS+) following ethanol. After pairing, the time spent with CS+ and CS- females was measured. WT(wt) females showed conditioned preference for the CS+ female paired with ethanol, demonstrated by greater interaction time (p<0.05). In both KO lines, ethanol significantly reduced interaction with the CS+ female (p<0.05), and there was no change in interaction for WT(ko) females. Response to odors by habituation-dishabituation was unaffected in both KO lines, and the response to a hypnotic dose of ethanol also was the same as in WT mice. However, anxiety, measured as time on the open arms of the elevated plus maze, was reduced in KO(Oxtr) females compared with WT(wt). The results suggest that Oxtr and Avpr1a are required for conditioned effects of an ethanol-associated social stimulus. The lack of CSP in WT(ko) females suggests that the quality of social interactions during postnatal and postweaning life may modulate development and expression of normal social responses.