Effects of the novel D1 dopamine receptor agonist ABT-431 on cocaine self-administration and reinstatement.

Abstract

Selective D1 dopamine agonists represent a potential pharmacotherapy for the treatment of cocaine addiction. Here we report that systemic injections of the novel D1 agonist ABT-431 lack the ability to induce cocaine-seeking behavior, and completely attenuate the ability of cocaine to induce this behavior in rats tested in a reinstatement paradigm. Similar doses suppress the initiation of cocaine self-administration, and produce an extinction-like response pattern in animals that subsequently initiate self-administration, without altering responding maintained by food pellets. There was no tolerance to this effect over 4 days of testing. The results suggest that ABT-431 attenuates the motivation to seek cocaine, and masks the reinforcing effects of cocaine during self-administration. The profile of ABT-431 is similar to the behavioral effects of other structurally distinct D1 agonists, and is consistent with the desired profile of a "methadone-like" compounds for cocaine addiction.