EFFECT OF COCAINE SELF-ADMINISTRATION ON STRIATAL DOPAMINE D-1 RECEPTORS IN RHESUS-MONKEYS

An array of evidence indicates that long-term exposure to cocaine alte rs several components of the brain dopamine system. Because the releas e of dopamine in the nucleus accumbens (NAc) has been implicated in me diating the reinforcing effects of cocaine, changes in dopamine functi on can have profound effects on drug-seeking and drug-taking behavior. The present study examined the effects of the chronic self-administra tion of cocaine on the D-1 family of dopamine receptors in the rhesus monkey. The brains of three rhesus monkeys that had intravenously self -administered an average of 1.35 mg/kg cocaine per day for 18-22 month s were compared to the brains of three cocaine-naive controls. The in vitro quantitative autoradiographic technique was used to quantify bin ding densities of the D-1 ligand [H-3]SCH-23390 on cryostat-cut sectio ns of fresh frozen tissue. In animals that self-administered cocaine, the density of D-1 binding was significantly lower in the regions of t he striatum at the level where the nucleus accumbens is most fully dev eloped. The shell of the NAc showed the largest difference with signif icantly lower D-1 binding also detected in adjacent regions of the cau date nucleus and the putamen. No differences were found in the rostral pole of the NAc or the dorsal striatum at that level. These findings suggest that chronic self-administration of cocaine can modulate the d ensity of dopamine D-1 receptors in specific portions of the primate s triatum. Such changes might underlie some of the behavioral consequenc es, like drug dependence and craving, of long-term cocaine use. (C) 19 98 Wiley-Liss, Inc.