Understanding the pharmacological mechanisms of relapse to cocaine-seeking behavior may facilitate the development of effective medications for cocaine abuse The present study investigated the role of D1- and D2-like dopamine (DA) receptor agonists using a nonhuman primate model of relapse Squirrel monkeys were trained to self-administer cocaine under a second-order fixed-interval fixed-ratio schedule Completion of each fixed-ratio produced a brief visual stimulus, and the first fixed-ratio completed after expiration of the FI produced an intravenous injection of cocaine paired with the stimulus Subsequently, animals underwent a period of extinction during which saline was substituted for cocaine and the cocaine-paired stimulus was omitted Following extinction, priming injections of cocaine and DA agonists, accompanied by restoration of the cocaine-paired stimulus, were assessed for their ability to reinstate extinguished cocaine-seeking behavior Cocaine -induced r einstatement was dose-dependent, approaching levels of responding similar to those maintained by cocaine self-administration Comparable to cocaine, the D2-like full agonists R(-)-propylnorapomorphine and quinpirole but not the D2-like partial agonists SDZ 208-911 and terguride induced robust reinstatement of drug-seeking behavior, and 7-OH-DPAT did so only in half of the subjects at the highest dose tested The D1-like full agonists SKF 81297 and SKF 82958 and partial agonists SKF 83959 and SKF 38393 did not mimic the priming effects of cocaine in any subject These results suggest that both receptor selectivity and intrinsic efficacy are relevant factors determining the ability of DA agonists to reinstate cocaine-seeking behavior and that D1- and D2-like receptor mechanisms play distinct roles in the relapse process PUBLICATIONS Spealman RD Relationships among discriminative stimulus, reinforcing, and relapse-inducing effects of cocaine Behav Pharmacol 9(Suppl 1):S122, 1998
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