BEHAVIORAL GENOMICS OF ALCOHOL NEUROADAPTATION

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project aims at understanding individual variation in risk for excessive drinking, with a focus on impulsive behaviors. A history of heavy ethanol intake appears to be related to increases in measures of impulsivity in humans. However human subject studies have been unable to distinguish antecedent baseline measures of impulsivity from the consequential effects of a history of heavy ethanol consumption. Our model of ethanol self-administration in cynomolgus monkeys provides a unique and important model of alcohol abuse, and reflects the individual differences in propensity to drink alcohol noted in the human population. Because of genetic similarities between humans and non-human primates, these studies can then be a key step in translating candidate mechanisms of ethanol's effects into the human condition through functional genomics. Thus, our primary focus of this PARC project is to use the monkey model to characterize antecedent and consequent measures of two aspects of impulsivity (the ability to rapidly stop, or withhold, responding and the aversion to a delay in reinforcement) with genetic factors related to excessive ethanol self-administration. Our Specific Aims are: (1) To determine if measures of impulsivity prior to alcohol exposure will predict chronic alcohol self-administration over a 12 month period;(2) To determine if chronic ethanol self-administration increases measures of impulsivity;and (3) To determine the expression of key gene networks in a brain area related to impulsive behaviors (the orbital medial prefrontal cortex) both prior to and following chronic alcohol drinking.