These findings demonstrate that U69593 attenuates cocaine self-administration and the reinstatement of drug-taking behavior which occurs in response to experimenter-administered cocaine. It is suggested that U69593 may decrease low dose cocaine self-administration by decreasing the priming effects of cocaine.

These findings suggest that cocaine seeking is only produced following administration of specific drugs. It is suggested that effective drug primes are those that produce a discriminative stimulus that generalizes to the stimulus produced by the reinforcing effects of cocaine.

The failure of U69593 to attenuate GBR 12909- or WIN 35,428-produced cocaine seeking suggests that the effect of this kappa-opioid receptor agonist on cocaine seeking is not mediated by interactions at the dopamine transporter. The ability of U69593 to attenuate RTI-55-produced cocaine seeking raises the possibility that kappa-opioids and cocaine may interact at common sites on the serotonin transporter.

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