The reality of ethanol exposure among children, from gestation through the infant, juvenile and adolescent periods, is supported by epidemiological evidence. The general purpose of this proposal is to study experimentally the nature and basis of early experiences with ethanol that potentiate responsiveness to ethanol later in life. The further purpose is to assess factors that may determine the persistence of these effects and lead, potentially, to increasing susceptibility to ethanol abuse in adolescence and adulthood. Three circumstances of early ethanol exposure will be studied, stated here in the form of three specific aims: (1) to determine the nature and short-term effects of perinatal learning involving ethanol's attributes, and persistence of the consequences of this learning. (2) To understand the nature and limits of short-term effects of a representative amount of ethanol during nursing, and the subsequent persistence of these effects. (3) To understand the nature and short-term effects of early ethanol ingestion (free or forced) as well as mere olfactory exposure to ethanol, and the persistence of these effects. Three sets of consequences of these effects will be assessed with established, largely behavioral tests. The first is alteration in efficacy in detection and perception of ethanol's orosensory attributes, assessed by cardiac orienting and basic behaviors indicating acceptance or rejection of ethanol. The second set assesses altered postingestive and pharmacological consequences of ethanol as well as acceptance of ethanol, in terms of ethanol-induced activation, tolerance to ethanol, and ethanol intake. The third set will determine changes in the reinforcing consequences of ethanol, in terms of conditioned place preference and operant responding for ethanol. The theoretical orientation is based on a model or metaphor of learning and memory, tested directly as part of Study 1, but the value of these studies is independent of the viability of this model. Persistence of the consequences of early ethanol exposure is studied with techniques based on those used previously to promote persistence of the consequences of another form of neuroplasticity, acquired memory. Preliminary studies indicate that persistence of the effects of early ethanol exposure may be promoted by similar principles, as a consequence of re-exposure to ethanol later in life.
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