Perhaps the best predictor of ethanol abuse in adolescence is prior fetal exposure. Further, there is an inverse correlation between the age of first experience and the likelihood of developing continued abuse. So, how does fetal exposure alter the acceptability of ethanol to adolescents? How does subsequent adolescent experience, following the fetal exposure, increase adult acceptance? Our novel central hypothesis is that fetal experience-induced plasticity, in response to ethanol, induces developmental changes in one or more of the chemosensory systems involved in the preference for ethanol odor and the perception of ethanol's flavor (the integration of odor, taste and somatosensation): thereby contributing to the risk of initial ethanol ingestion and continued adolescent abuse. We also propose that further ethanol experience during adolescence augments and/or perpetuates the chemosensory effects of fetal exposure, resulting in persistence into adulthood. This proposition is supported by our prior studies and compelling PRELIMINARY DATA demonstrating that clinically relevant fetal exposure to ethanol results in: (1) a tuned neural and behavioral olfactory response to ethanol odor and enhanced ethanol intake in the early postnatal animal that persists into adolescence, yet is absent in adults;(2) enhanced taste-mediated orosensory responsiveness to ethanol in adolescent animals that, in parallel with the olfactory system response, is absent in adults;and (3) that adolescent re-exposure augments the olfactory behavioral response resulting from the prior fetal experience. Our work reveals two chemosensory mechanisms by which fetal exposure enhances ethanol preference and intake. Our long-range goal is to understand how fetal and adolescent ethanol experience impacts the behavioral response to ethanol odor, the perception of ethanol's flavor and the acceptance of the drug;and to understand the chemosensory mechanisms underlying these effects. Applying behavioral, neurophysiologic and anatomical methods, the objectives of this proposal are to determine the impact of fetal and adolescent ethanol experience on adolescent: (1) olfactory system function and ethanol intake;(2) taste-mediated orosensory responses to (and flavor perception of) ethanol and its component qualities (sweet, bitter and irritancy);and (3) the persistence of these effects into adulthood. We will determine whether the neurophysiologic and anatomical effects mediate the behavioral response of the animal. This research is significant - it is expected to: advance our understanding of factors contributing to the initiation of ethanol ingestion and preference during adolescence, and the clinical progression into adult abuse (The Alcoholism Generator)] facilitate the development and testing of preventive and therapeutic strategies;and establish a chemosensory related conceptual framework of fetal and adolescent exposure with broad importance for child development, drug abuse, and environmental health and safety.
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