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Science 18 June 1993:
Vol. 260. no. 5115, pp. 1814 - 1816
DOI: 10.1126/science.8099761
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Articles

Science, Vol 260, Issue 5115, 1814-1816
Copyright © 1993 by American Association for the Advancement of Science

articles

Modulation of cocaine self-administration in the rat through D-3 dopamine receptors

SB Caine and GF Koob

Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.

The reinforcing properties of cocaine are probably mediated by the mesocorticolimbic dopamine pathways in the central nervous system, but not all of the dopamine receptor subtypes involved in cocaine's reinforcing actions have been clearly identified. Recently, the D-3 receptor has been cloned, and its distribution in the brain has been found to be relatively restricted to limbic projections of the midbrain dopamine system. The D-3-selective compounds 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT) and quinpirole potently decreased cocaine self-administration in the rat at doses that were not by themselves reinforcing. Moreover, three dopamine receptor agonists had affinities for binding to the D-3 receptor that correlated highly with their relative potencies in decreasing cocaine self-administration. The D-3 receptor may be involved in the reinforcing effects of cocaine and may be a useful target for the development of new pharmacotherapies for cocaine abuse.


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