EFFECT OF COCAINE SELF-ADMINISTRATION ON DOPAMINE D-2 RECEPTORS IN RHESUS-MONKEYS

The present study used autoradiography to examine the effects of chron ic self-administration of cocaine on the density of dopamine D-2 recep tors in nonhuman primates. Three rhesus monkeys intravenously self-adm inistered an average of 1.35 mg/kg cocaine per day for 18-22 months un til they were euthanized immediately after a self-administration sessi on. Binding site density of the D-2 ligand [H-3] raclopride (2 nM) was assessed in these monkeys as well as three untreated controls, using quantitative in vitro receptor autoradiography. As compared to untreat ed controls, D-2 binding site density was significantly lower in the a nimals that self-administered cocaine in all regions of the striatum r ostral to the anterior commissure. These regions include the anterior and central regions of the caudate nucleus, putamen, olfactory tubercl e, and both the shell and core of the nucleus accumbens. Within the su bstantia nigra and Ventral tegmental area, by contrast, no differences were found in the density of D-2 binding sites. These findings sugges t a pervasive effect of cocaine on the regulation of D-2 receptors in the striatum. The lack of change within the ventral midbrain, however suggests a differential regulation of D-2 receptors in the striatum an d ventral midbrain. This study confirms and extends our knowledge of t he neurobiological changes in the mesolimbic dopamine system that resu lt from chronic exposure to cocaine. Synapse 30:88-96, 1998. (C) 1998 Wiley-Liss,Inc.