Effects of Cocaine Self-administration on Striatal Dopamine Systems in Rhesus Monkeys: Initial and Chronic Exposure

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 27; no. 1; pp. 35 - 46
• Main Authors: Nader, Michael A, Daunais, James B, Moore, Tonya, Nader, Susan H, Moore, Rodney J, Smith, Hilary R, Friedman, David P, Porrino, Linda J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2002; Nature Publishing; Nature Publishing Group
• Subjects: Animals; Binding Sites - drug effects; Biological and medical sciences; Cocaine; Cocaine - administration & dosage; Cocaine abuse; Corpus Striatum - drug effects; Corpus Striatum - metabolism; D1 receptors; D2 receptors; Dopamine; Dopamine D2 Receptor Antagonists; Dopamine Uptake Inhibitors - administration & dosage; Drug addictions; Drug dosages; Drug withdrawal; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Macaca mulatta; Male; Medical sciences; Monkeys & apes; Nucleus accumbens; Receptors, Dopamine - metabolism; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - biosynthesis; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - biosynthesis; Receptors, Dopamine D2 - metabolism; Rhesus monkey; Self Administration; Striatum; Toxicology; Nucleus accumbens; Striatum; Rhesus monkey; Cocaine abuse; Dopamine; D1 receptors; D2 receptors; Drug addiction; Intravenous administration; CNS stimulant; Illicit drug; Psychotropic; Toxicity; D1 Dopamine receptor; Monkey; Central nervous system; Molecular interaction; Corpus striatum; Self administration; Ester; Vertebrata; Mammalia; D2 Dopamine receptor; Animal; Primates; Cocaine; Drug of abuse; Mechanism of action; Dopaminergic pathway; Brain (vertebrata)
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(01)00427-4

The purpose of this study was to examine the time course of changes in dopamine D1- and D2-like receptor densities in monkeys self-administering cocaine. Experimentally naı̈ve 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 ∼100 sessions). After the last session, monkeys were euthanized, brains were removed, frozen, and coronal sections through the striatum, rostral to the anterior commissure, were processed for D1 ([3H]SCH23390) and D2 ([3H]raclopride) receptor autoradiography. Compared with controls, there was no effect of 5 days of cocaine self-administration on D1 and D2 receptors. In monkeys with extensive cocaine histories, D1 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.