Behavioral Toxicity of Chronic Alcohol Drinking in Peri-Adolescent Monkeys

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DESCRIPTION (provided by applicant): Recreational overuse of alcohol among adolescent populations remains a significant and growing public health concern. Surveys report that 10% of eighth graders and up to a third of high school seniors consume binge quantities (5 drinks or more) of alcohol on a weekly basis. Heavy drinking during this critical period of formal education and significant brain development may pose serious risk for later intellectual and cognitive function. The proposed studies will use a nonhuman primate model to evaluate the consequences of heavy drinking during adolescence task acquisition and performance in a range of cognitive domains. The project seeks to determine the cognitive domains which are impaired by chronic oral alcohol intake; contributions of impulsivity, alcohol preference and serotonin transporter genotype to behavioral change; and the cognitive and behavioral effects of withdrawal from chronic alcohol exposure in periadolescent monkeys. These studies follow an Exploratory/Developmental project (R21 AA013972, 02/05/04-01/31/07) in which it was established that male monkeys consuming alcohol are impaired in acquiring a visuo-spatial paired-associates learning task and in performing the spatial delayed-response task of spatial working memory. Alcohol-exposed animals appeared unimpaired on discrimination learning and long-term memory tests suggesting an effect which may be selective for specific cognitive domains. The proposed studies will use an established procedure to generate consistent, high levels of alcohol drinking in the experimental groups which will be allowed to orally self-administer alcohol (M-F) for 24 months. The experimental groups and control group monkeys will be concurrently trained on a comprehensive battery of tests (derived in part from the human CANTAB) which probe multiple aspects of learning, memory, attention and motor functions. It is hypothesized that tasks which depend more on frontal-type executive function will be preferentially affected by chronic alcohol drinking. It is further predicted that cognitive differences attributable to alcohol will be maintained upon long-term removal of access to alcohol. PUBLIC HEALTH RELEVANCE: Alcohol remains the most abused psychoactive drug in adolescents with up to half of 12th graders reporting consumption in the past 30 days. The majority of alcohol using 12th graders report at least one heavy drinking episode (5 drinks or more) in the prior two weeks. Adolescence is a critical time for both brain development and the acquisition and refinement of many cognitive skills necessary for vocational success. These studies seek to identify the mechanisms by which alcohol drinking can interfere with learning, memory, attention and other critical cognitive functions.