The interaction of sex and route of drug administration in cocaine-induced conditioned taste aversions

Although taste aversion learning has been reported to be a function of a variety of factors, one that has received considerable attention is the subject's sex, wherein males generally display stronger taste aversions than females. An exception to these findings is with cocaine for which females have been shown to display greater aversions than males. Although suggestive of a Sex × Drug interaction, cocaine was administered subcutaneously (SC) in this report while others administered drug intraperitoneally (IP). Thus, there may be a Sex × Route interaction. To address the contributions of sex and route in cocaine aversions, the present study examined aversions in male and female Sprague-Dawley rats administered a range of doses of cocaine either SC or IP. At the two higher doses of cocaine tested (20 and 32 mg/kg), aversions were a function of route with animals injected SC with cocaine displaying greater aversions than those injected IP. Although there was no main effect of sex at either dose there was an interaction between sex and route at the 20 mg/kg dose. Specifically, SC-injected males displayed stronger aversions than IP-injected males. There were no differences between the two routes for females. Further, males displayed stronger aversions than females when injected SC. There was no sex difference when both groups were injected IP. This interaction was no longer evident at the highest does of cocaine (32 mg/kg). These data indicate that sex differences in aversion learning with cocaine are a function of the route of cocaine administration (and are dose specific).