Chronic intermittent ethanol treatment yields persistent increases in anxiety and receptor subunit changes in adolescent and adult rats.
Van Skike, Candice E.
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GABAA and NMDA receptors are involved in the behavioral effects of ethanol; however, the age-dependent molecular mechanisms associated with the effects of chronic ethanol have yet to be fully elucidated. Adolescence is marked by unique sensitivity to certain effects of ethanol, including distinct consumption patterns, increased prevalence of consumption during young adulthood compared to that of abstaining adolescents, and increased risk for development of future alcohol use disorders. In the adult, tolerance and dependence are marked by attenuated function of GABAA receptors and increased function of NMDA receptors, but the receptor subunit expression profiles for adolescents following binge-like ethanol exposure are not yet completely known. Since tolerance and withdrawal appear to be age dependent, it is likely that receptor subunit expression is differentially altered following chronic ethanol exposure in adolescence compared to adulthood. Additionally, chronic ethanol exposure and its withdrawal can alter behavior. Especially relevant to the maintenance and persistence of consumption behaviors are alterations in anxiety. Anxiety levels can often be used to predict relapse in detoxified alcohol-dependent patients long after ethanol cessation, therefore it is important to determine the persistence of the anxiogenic effects of ethanol withdrawal and how alterations in receptor subunits may interact with withdrawal-induced anxiogenesis. Given that very little research has focused on age dependent anxiogenesis and subunit alterations following chronic ethanol consumption, this project will investigate multiple withdrawal induced changes in anxiety and its persistence in adolescent and adult rats. Additionally, the persistence of any changes in receptor subunit expression will be assessed using the same animals from the anxiety data. This multimodal, within-subjects design allows for the direct exploration of the relationship between behavioral and molecular alterations due to chronic ethanol exposure.