Abstract
BACKGROUND: Withdrawal from an acute high ethanol dose induces behaviors reminiscent of withdrawal from chronic ethanol exposure. While such "hangover"-related anxiety has previously been shown to be considerably less pronounced in adolescent compared to adult male rats, ontogenetic studies are limited and few experiments have directly compared sex- and age-related differences in sensitivity to ethanol hangover. METHODS: The current experiments examined consequences of a previous ethanol challenge (4.0 g/kg i.p. injection, 20% v/v) on anxiety and exploratory behavior in the elevated plus-maze (EPM) and holeboard (HB) tests, respectively, in adolescent and adult male and female Sprague-Dawley rats. RESULTS: In Exp. 1, evidence of hangover-related anxiety and withdrawal-induced hypoactivity emerged at both ages and in both sexes. As several procedural variables were changed in Exp.1 relative to previous studies from our laboratory showing age-related differences in these hangover measures, Exp. 2 explored the possible contribution of 2 variables to ontogenetic expression of withdrawal-induced anxiogenesis: (1) isolation vs. social context during the postchallenge recovery period and (2) EPM testing alone or immediately following a 5 minute HB test. Results of Exp. 2 revealed few significant interactions of these variables with age- and ethanol exposure-related anxiety measures, although sequential testing (HB before EPM) notably suppressed activity in the EPM and altered the major underlying component of EPM behavior from anxiety to activity as revealed in factor analyses of these data. Additional analyses conducted on animals tested only in the EPM revealed attenuations in withdrawal anxiogenesis among adolescents, along with withdrawal-related decreases in activity at both ages. CONCLUSIONS: Taken together, these results suggest that adolescents do show an attenuated sensitivity to hangover-induced anxiogenesis in the EPM, an age difference not evident under other pretest conditions. Therefore, caution should be exerted when using the EPM to index anxiety across age. The robustness of withdrawal-related hypoactivity at both ages suggests that adolescents may not be globally insensitive to the consequences of previous binge-like exposure to ethanol, but rather less likely to express certain hangover-related consequences.