Adolescents differ from adults in responsivity to a number of ethanol effects. Their insensitivity to the motor incapacitating and sedating effects of ethanol may increase consumption capacities and support higher levels of adolescent drinking, thereby contributing to the unique risks associated with alcohol drinking during adolescence. It has yet to be established whether this unique pattern of alcohol responsivity during adolescence is a function of age-related differences in initial neural sensitivity to alcohol or in the magnitude of tolerance developing within ethanol exposure periods (acute tolerance) or across exposures (rapid and chronic tolerance). There are, however, recent observations of notable ontogenetic alterations in the expression of these ethanol adaptations. Such ontogenetic differences in ethanol tolerance may be particularly pronounced under stressful circumstances, given evidence that vulnerability to stressors may be increased during adolescence and that development of ethanol tolerance is enhanced by stressors. Consequently, the work outlined in this proposal will explore the contribution of tolerance to the unique pattern of alcohol responsivity during adolescence, and the effects of stressors on these adaptational processes. Studies will compare the expression of acute, rapid and chronic tolerance to various characteristic effects of ethanol and the impact of stressors on these ethanol adaptations in male and female, adolescent and adult (as well as weanlings, where feasible) Sprague-Dawley rats. It is predicted that age-related attenuations in sensitivity to specific ethanol effects will be associated with greater acute tolerance but less rapid and chronic tolerance to those effects, with adolescents being particularly vulnerable to stress-induced facilitation of acute, rapid and chronic tolerance. Characterizing the ontogeny of ethanol tolerance and the effects of stressors on these adaptational processes is not only critical for assessing determinants of the unique pattern of alcohol responsivity seen during adolescence, but also may contribute to our understanding of the long-term consequences of adolescent alcohol exposure for later alcohol use and abuse.
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