Use of ethanol during or just before adolescence clearly predicts ethanol abuse later in life. Is this ethanol use in adolescence due to still earlier exposure to ethanol? Epidemiological evidence in humans and experiments with rats indicate that ethanol acceptance in adolescence is potentiated by prenatal exposure to ethanol. The present proposal tests the hypothesis that a few moderate, nonteratological doses of ethanol during late gestation alters later responsiveness to ethanol, including ethanol acceptance and reinforcement from birth to adolescence and activating effects of ethanol during adolescence. This hypothesis is encouraged by preliminary studies indicating that this prenatal ethanol exposure not only increases later ethanol acceptance but also increases the range of appetitively reinforcing ethanol doses. In each of the proposed experiments postnatal responsiveness to ethanol will be assessed for animals given 0, 1 or 2 g/kg on each of gestational days 17-20 or a control treatment.
Specific Aim 1 is to test ethanol intake and ethanol reinforcement soon after birth, in terms of three different reinforcement paradigms.
Specific Aim 2 is to test effects of .prenatal ethanol on ethanol acceptance and ethanol reinforcement in adolescence and at a point midway between birth and adolescence (postnatal day 15, P15).
Specific Aim 3 is to test the consequences of prenatal ethanol exposure for an established activating effect of ethanol during adolescence, ethanol- induced social facilitation. In view of the apparent role of the endogenous opioid system in ethanol ingestion, ethanol reinforcement and adolescent social behavior, Specific Aim 4 is to test the effects of prenatal ethanol on beta-endorphin gene expression, beta-endorphin brain levels and ?-opioid receptor binding associated with ethanol ingestion, ethanol reinforcement, and ethanol-induced social behavior. These tests will occur soon after birth, on P15 or during adolescence. The intention is to clarify the ontogeny of risk from moderate exposure to prenatal ethanol and determine mechanisms underlying subsequently altered responsiveness to ethanol. *Proposed experiments will test the observation that individuals exposed to ethanol as fetuses are more likely to abuse ethanol as adolescents and adults, whether this fetal exposure makes ethanol more rewarding and acceptable later on, and how these effects might be mediated by the opiate system.
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