Deficits in decision-making underlie numerous components of the addiction cycle including a lack of behavioral control in daily function as well as compulsive and uncontrollable alcohol consumption and relapse. In order to understand how these deficits contribute to addiction, it is necessary to understand the basic decision-making mechanisms disrupted in dependence. One of the key brain regions involved in decision- making is the orbital frontal cortex (OFC). Despite widespread reports of dependence-induced alterations in OFC function, relatively little is known in regards to how alcohol dependence affects OFC involvement in decision-making. At the heart of the problem lies the fact that OFC is widely connected to the rest of the brain and has been suggested to play a role in numerous behavioral processes. Thus relatively little is known about specific OFC decision-making processes disrupted in alcohol dependence and the OFC circuits disrupted. This proposal will use an integrative approach to directly assess effects of alcohol dependence on identified OFC circuits controlling isolated goal-directed decision-making processes. By combining sophisticated behavioral tasks with cutting edge cell-type and circuit specific in vivo and ex vivo manipulations and measurements in a well-validated model of alcohol dependence and alcohol self-administration, this proposal will 1) identify behavioral mechanisms that contribute to dysfunctional goal-directed decision-making, 2) define the contributing OFC circuits disrupted in dependence, and 3) determine populations downstream from OFC controlling the aberrant decision-making observed following dependence. These experiments will test the central hypothesis that alcohol dependence alters orbital cortex function and output thereby resulting in dysfunctional value-based decision-making. The proposed studies are expected to significantly advance our understanding of how alcohol dependence alters decision-making. Insights in to the specific decision-making and associated neural mechanisms altered are expected to directly lead to testable hypotheses in the restoration of behavioral control over alcohol consumption and relapse.
Identifying how alcohol dependence disrupts decision-making is a key first step toward understanding how impaired executive function contributes to chronic alcohol use, abuse, and relapse. A better understanding of circuits and mechanisms disrupted by chronic alcohol exposure will be significant as it has the potential to direct new strategies aimed at restoring proper decision-making for the treatment of alcohol addiction.
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