In humans, a strong association between anxiety and alcohol use has been reported among adolescents. Enhanced vulnerability to both anxiety and alcohol use disorders in adolescence is frequently associated with prenatal alcohol exposure, however, the mechanisms contributing to this enhanced vulnerability in adolescents prenatally exposed to alcohol remain poorly understood. A main limitation of the human data is that much of the research has involved self-report questionnaires, which limits causal interpretation of the results and does not permit systematic manipulation of critical variables, due to ethical considerations. Therefore, animal models are of particular importance. The proposed studies will use a simple rat model of social anxiety induced by acute prenatal ethanol exposure to assess responsiveness to social stressors and ethanol sensitivity in adolescents with the social inhibition and/or social avoidance phenotype. Offspring tested in adulthood will be included to assess persistence of alterations in stress responsiveness and ethanol sensitivity. The proposed research will address the following aims: (1) test whether the social avoidance phenotype induced by prenatal ethanol exposure is associated with enhanced stress responsiveness;(2) test whether (a) sensitivity to ethanol-induced social facilitation and ethanol-induced anxiolysis and (b) intake of ethanol under social circumstances are enhanced following prenatal ethanol exposure;(3) test whether the social avoidance phenotype induced by prenatal ethanol exposure is associated with alterations in structural plasticity in the neurocircuitry implicated in stress and anxiety. These studies will provide critical new information regarding mechanisms involved in vulnerability to affective and alcohol use disorders among adolescents exposed to alcohol prenatally. Understanding of these mechanisms is essential for creating new prevention and intervention strategies as well as new approaches to pharmacological treatment of alcohol use disorders during adolescence.
Prenatal alcohol exposure increases the risk of anxiety and alcohol use disorders later in life, conditions with considerable effects on health, society and the economy. The proposed work will expand our understanding of mechanisms leading to anxiety and alcohol use disorders in adolescents prenatally exposed to alcohol and will help to more effectively prevent prenatal alcohol exposure and treat its consequences.
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