The purpose of this study was to examine the time course of changes in dopamine D-1- and D-2-like receptor densities in monkeys self-administering cocaine. Experimentally naive adult male rhesus monkeys (n = 22) were divided into a food reinforcement group (n = 6), in which responding was maintained by food presentation, or into four cocaine self-administration groups (n = 4/group), based on dose (0.03 or 0.3 mg/kg per injection) and duration of exposure (5 or similar to100 sessions). After the last session, monkeys were euthanized, brains were removed, frozen, and coronal sections through the striation, rostral to the anterior commissure, were processed for D-1 ([H-3]SCH23390) and D-2 ([H-3]raclopride) receptor autoradiography. Compared with controls, there was no effect of 5 days of cocaine self-administration on D, and D2 receptors. In monkeys with extensive cocaine histories, D, receptor densities were significantly increased relative to controls in some parts of the striatum, while D2 receptor densities were significantly decreased throughout the striatum. These findings demonstrate that chronic cocaine self-administration produces neuroadaptations in dopamine systems, but that these changes do not occur in a parallel fashion. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.