Age differences in ethanol discrimination: Role of GABA-A and NMDA receptors

State University Of Ny,Binghamton, Binghamton NY

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Abstract

Adolescence is a developmental period during which high ethanol use is common. Studies using rodent models of adolescence have observed age-related differences in sensitivity to many of ethanol's properties, including greater sensitivity of adolescents than adults to ethanol-induced social facilitation, but attenuated sensitivity to ethanol- induced motor impairment, sedation, and dysphoria. Such age discrepancies in sensitivity suggest that adolescents and adults may perceive ethanol's subjective effects differently. Ethanol discrimination procedures have been used extensively to gain insight into the interoceptive (i.e., subjective) properties of ethanol, but studies using such procedures have largely neglected adolescent subjects. Using an established animal model of adolescence, the proposed work aims to characterize the ethanol cue in adolescent rats relative to adults using a Pavlovian conditioned approach drug discrimination procedure amenable to testing animals within the relatively short developmental period of adolescence. This procedure will allow for comparison of discrimination acquisition in adolescents and adults under a variety of training conditions that will take into account age differences in ethanol sensitivity. Given that GABAA and NMDA receptor systems have been identified as major contributors to the ethanol cue in adult animals, psychopharmacological studies will then examine the role of developmental alterations in GABAA and NMDA subunit composition in the ethanol cue in animals of each age by testing subunit-specific compounds in ethanol substitution tests and quantifying subunit expression in specific brain regions across age using both mRNA and protein assays.