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.

• Authors: D W Self, D A Karanian, J J Spencer
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 909 Pg. 133-44 ( 2000) ISSN: 0077-8923 [Print] United States
• PMID: 10911927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Pyridines
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• Tetrahydronaphthalenes
• adrogolide hydrochloride
• Cocaine

Topics

• Animals
• Cocaine (administration & dosage)
• Cocaine-Related Disorders (drug therapy)
• Conditioning, Psychological (drug effects)
• Male
• Pyridines (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine D1 (agonists)
• Receptors, Dopamine D2 (drug effects)
• Tetrahydronaphthalenes (therapeutic use)