High levels of ethanol (EtOH) consumption during adolescence may be in part biologically driven, given that adolescents often manifest 2-3 fold greater EtOH intakes than adults in a variety of mammalian species. Studies in rats have suggested that such elevated intakes may be possible in part because adolescents are less sensitive than adults to aversive effects of EtOH and other intoxicating effects that may normally serve as cues to moderate intake. Genetic studies have found that sensitivity to aversive effects of EtOH plays an important role in moderating EtOH intake, and is more strongly related to EtOH intake than sensitivity to EtOH's rewarding properties. Despite compelling evidence for an association between insensitivity to EtOH aversion and enhanced EtOH intake, little is known about the ontogeny of these aversive sensitivities, their regional specificity and neural contributors. In conjunction with the DEARC NeuroCore and Animal/Behavior Core, the proposed work will address these critical gaps.
Aim 1 will use conditioned taste aversions (CTA) to examine the ontogeny of the developmental insensitivity to EtOH's aversive effects throughout the juvenile to adult period.
Aim 2 will assess c-Fos activation patterns to aversive effects of EtOH across age and associate these activation patterns with age differences in EtOH aversion. Focusing on an aversive region where activation is strongly linked to age differences in EtOH CTA, Aim 3 will determine whether reversible inactivation of that region diminishes age differences in EtOH's aversive effects and EtOH intake differences, while Aim 4 will examine potential neural substrates underlying the age differences in EtOH-induced activation in this region via examination of NMDA, GABA and opiate receptor regulation and intracellular signaling pathways.
Aim 5 will determine whether elevations in adolescent drinking induced by prenatal EtOH exposure are accompanied by exacerbated insensitivies to EtOH's aversive effects. Collectively, these studies will provide critical new information to further our understanding of how ontogenetic changes in the brain contribute to adolescent insensitivities to aversive properties of EtOH, and ultimately to the elevated levels of EtOH drinking characteristic of adolescence.
Adolescent alcohol use Is high, with adolescents across species ranging from humans to rodents often consuming 2-3 times more alcohol per occasion than adults. These elevated intakes appear related in part to an adolescent insensitivity to aversive effects of alcohol that seemingly serve to temper intake. This project assesses how the developing brain contributes to the resistance of adolescents to alcohol's aversive effects, information that may ultimately prove critical for reducing excessive adolescent alcohol use and later abuse.
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