GRANT NUMBER: R01 DA033358-02S1  

ABSTRACT: Drug addiction is a brain disorder characterized by a progression toward compulsive drug use and relapse to drug seeking during abstinence. Polysubstance use and abuse can a critical factor in the initiation, maintenance and drug seeking that characterize this disorder. The primary goal of this supplement research proposal is to explore the neurobehavioral consequences of the combined use of alcohol and methamphetamine. Epidemiological studies suggest that the co-use of these substances is significant, yet there is little basic research addressing how methamphetamine and alcohol interact behaviorally or impact neurobiological systems. We will investigate whether the combined use of methamphetamine and alcohol interact behaviorally to enhance the intake and relapse of either substance and identify how the combined use affects synaptic adenosine receptor expression and the heteromeric complexes of adenosine and dopamine receptors within the striatum. Throughout these studies, we will utilize the selectively bred high alcohol preferring (P) rats to model high alcohol users and Sprague-Dawley rats to model low alcohol users. In Aim 1, experiments will assess whether alcohol drinking alters methamphetamine reward, reinforcement and relapse. We will also explore whether methamphetamine self-administration alters alcohol drinking in both high alcohol consuming P rats and low alcohol consuming SD rats. As part of the parent award, we have determined that methamphetamine self-administration decreases the expression of both adenosine A1 and adenosine A2A receptors in the nucleus accumbens. The studies in Aim 2 will complement these findings by identifying whether the combined use of alcohol drinking and methamphetamine self-administration exacerbate these decreases or produce changes that offset methamphetamine-induced decreases. Additional experiments in Aim 2 will identify how the combined use of methamphetamine and alcohol alters the heteromeric receptor complexes that adenosine receptors form with dopamine receptors in the striatum. Together the studies from Aim 1 and 2 will provide results from fundamental behavioral tests that will identify how the combined use of alcohol and methamphetamine may promote addiction and explore potential mechanisms by which these behavioral alterations may occur.


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