BASOLATERAL AMYGDALA AND COCAINE SEEKING

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (provided by applicant) The long-term goal of our research is to investigate neural mechanisms that mediate drug addiction relapse. Cocaine addicted individuals frequently return to compulsive drug taking after periods of abstinence and despite severe adverse consequences. Identification of the variables that cause a drug-free addicted individual to initiate drug seeking is critical to the development of relapse prevention treatments. Although initiation of drug seeking by drug-free addicts is influenced by a variety of factors, it appears to be controlled importantly by stimuli that are associated with addictive drugs through classical conditioning mechanisms. Understanding the neural mechanisms that mediate this stimulus control of drug seeking could aid in the development of treatments. Our research will test three hypotheses related to this therapeutic endpoint. First, we will test the hypothesis that the basolateral nucleus group of the amygdala (BLNG) contributes to stimulus-control of drug seeking. We will test this hypothesis by using chronic extracellular recording techniques to test for BLNG responses to cues that have been associated with cocaine and that maintain cocaine seeking in the absence of drug. The second hypothesis that we will test is that BLNG neurons encode the association between conditioned stimuli and the rewarding properties of addictive drugs. To test this proposal we will determine whether BLNG neural responses to conditioned stimuli are sensitive to the value of the cocaine reward associated with the cues. Finally, the third hypothesis that we will examine is that disruption of BLNG neural responses to conditioned drug stimuli mediates the potential therapeutic effects of the partial D3 dopamine agonist BP 987. This drug selectively disrupts control of cocaine-seeking behavior by conditioned stimuli and might therefore be useful as a relapse prevention medication in human cocaine addicts. To test this hypothesis we will evaluate the effects of various doses of BP 987 on the BLNG neural responses to conditioned stimuli. If the BLNG is involved in the BP 987 effects, the BLNG responses to conditioned drug stimuli should be diminished in conjunction with the agonist-induced disruptions in stimulus-controlled behavior. The results of these novel recording studies are expected to inform us about the proposed role of the BLNG in regulation of stimulus controlled drug seeking and to additionally inform us about the mechanisms that mediate the potential therapeutic effects of one of the most promising cocaine relapse prevention pharmacotherapies currently being evaluated in basic research.