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Prior activation of the kappa opioid system by repeated stress or agonist administration has been previously shown to potentiate the rewarding properties of subsequently administered cocaine. In the present study, intermittent and uncontrollable footshock, a single session of forced swim, or acute administration of the kappa agonist U50,488 (5 mg/kg) were found to reinstate place preference in mice previously conditioned with cocaine (15 mg/kg) and subsequently extinguished by repeated training sessions without drug.

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system