Role of MOR1 up-regulation in relapse to cocaine seeking

Ut Southwestern Medical Center, Dallas TX

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Abstract

DESCRIPTION (provided by applicant): Relapse behaviors associated with increasing periods of withdrawal from chronic cocaine self-administration. Previous studies find a relationship between the upregulation of MOR1 and cocaine administration. Using the cocaine self-administration model in rodents, the proposed study plans to determine the time-frame of functional MOR1 upregulation in nucleus accumbens (NAc) during withdrawal from chronic cocaine selfadministration using Western blot of opioid receptors and activation of receptor downstream targets and behavioral responses to opioid stimulation during withdrawal. In addition, this study will pharmacologically investigate the role of MOR1 in NAc core and shell in modulating relapse behavior in animals undergoing a within-session reinstatement paradigm using opioid receptor agonists and antagonists. Viral- mediated MOR1 overexpression and knock-down will be used to study MOR1 effects on cue-, stress-, and drug-induced relapse. This study may elucidate new strategies for the treatment or the prevention of neuroadaptations that increase the propensity for relapse in drug addicted individuals.