The consequences of positive and negative ethanol reinforcement vary during development. The present proposal tests the hypothesis that positive and negative reinforcements are differentially affected by controlling parameters. Moreover, there is further value in comparing the efficacy of ethanol reinforcement between the second postnatal week and late adolescence. (1) In humans and animals, exposure to ethanol during the early part of this period increases affinity for ethanol during adolescence. (2) As infant rats ingest ethanol in substantial quantities without initiation procedures (like adult rats selectively bred for high initial acceptance of ethanol), they provide an alternative to the use of genetic selection for determining mechanisms of ethanol reinforcement. That is, tests with the developmental model hold the genetic potential constant while varying age, whereas tests with a genetic model hold age constant while varying genetic potential. (3) Although the critical period of adolescence for determining ethanol abuse in humans has become better understood by contrasting the sensitivity of adolescent and adult rats to ethanol, it remains uncertain whether ontogenetic progression into these aspects of adolescence is abrupt, a discrete break from earlier ages, or continuous. Presumably then, younger animals should have vestiges of mechanisms responsible for the adolescent's sensitivity to ethanol and susceptibility to ethanol abuse. Thus, the proposed studies will examine the ontogeny of positive and negative ethanol reinforcement between, the effect of earlier exposure to ethanol on positive and negative ethanol reinforcement in late adolescence, and explore central mechanisms underlying negative and positive reinforcement. Psychopharmacological experiments will examine receptor systems that change ontogenetically and have strong theoretical and empirical links to negative or positive reinforcement. These studies will be supported by collaborations with the CELL/MOLECULAR BIOLOGY CORE, to assess translational and protein expression of localized mu opioid receptors and three GABAA receptor subunits (2, 3, and 5) in response to the ethanol reinforcement; and with the NEUROANATOMY CORE, to determine the number of neurons expressing, in selected neural areas, cFos in response to the early ethanol exposure that is expected to alter ethanol reinforcement in late adolescence. A key feature of these experiments is application of tests for negative and positive reinforcement that are comparable over the range of ontogeny. The proposed experiments will clarify the relationship between early ethanol exposure and the 'early debut' effect in humans. Clinical benefits may occur in terms of determining the need for differential treatment for ethanol abuse originating primarily from positive or negative reinforcement sources, the role of pre-adolescent ethanol experience, and the potential interaction between age and 'type' of ethanol reinforcement that dominates one's experience.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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State University of NY, Binghamton
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