Infralimbic Regulation of Memory Consolidation of Extinction of Cocaine-seeking

Medical University Of South Carolina, Charleston SC

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Abstract

DESCRIPTION (provided by applicant): Cocaine addiction is a serious problem afflicting the United States, and treatment remains imperfect. Although the study of cocaine self-administration and reinstatement in rats has provided much knowledge of cocaine addiction, relatively few studies have explored the extinction of self-administration behavior in rats. Nonetheless, the extinction of cocaine self- administration provides a major potential pharmacotherapeutic target in the effort to reduce relapse to cocaine use. Therefore, the long-term objective of the proposed work is to investigate the neurobiology of extinction of cocaine self-administration and determine whether infralimbic cortical activity can be modulated to influence memory consolidation of extinction training. Previous findings, together with preliminary data, suggest that a circuit involving the infralimbic cortex regulates the memory consolidation of extinction of cocaine self-administration. The proposed experiments will use male Sprague-Dawley rats that will undergo cocaine self- administration followed by extinction. Rats will receive microinjections immediately AFTER extinction sessions on days 1-5 of extinction training. Specific Aim #1 will examine how inactivation of the infralimbic cortex immediately after extinction training sessions influences the retention of the extinction training. Specific Aim #2 will investigate whether blockade of 2- adrenergic receptors in the infralimbic cortex immediately after extinction training sessions impairs memory consolidation of that training. Specific Aim #3 will examine whether activation of 2-adrenergic receptors in the infralimbic cortex immediately after extinction training sessions enhances memory consolidation of that training. Together, these experiments will provide important new information on the circuitry underlying the learning and memory of extinction of cocaine self-administration and how 2-adrenergic receptor blockade and activation in the infralimbic cortex modulate memory consolidation of extinction training. Cocaine addiction remains a significant problem, in large part due to the high rate of relapse following treatment. The proposed research will investigate the neurobiology of the extinction of cocaine self-administration in rats. This research will have a significant impact on public health as the extinction process is a potential pharmacotherapeutic target in the treatment of drug addiction.