Adolescent rats are resistant to the development of ethanol-induced chronic tolerance and ethanol-induced conditioned aversion

Abstract

The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake.