Effects of cocaine self-administration on striatal dopamine systems in rhesus monkeys: initial and chronic exposure.
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 naïve 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 approximately 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 D(1) ([3H]SCH23390) and D(2) ([3H]raclopride) receptor autoradiography. Compared with controls, there was no effect of 5 days of cocaine self-administration on D(1) and D(2) receptors. In monkeys with extensive cocaine histories, D(1) receptor densities were significantly increased relative to controls in some parts of the striatum, while D(2) 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.
Nader
Michael A
MA
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. mnader@wfubmc.edu
Daunais
James B
JB
Moore
Tonya
T
Nader
Susan H
SH
Moore
Rodney J
RJ
Smith
Hilary R
HR
Friedman
David P
DP
Porrino
Linda J
LJ
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000378:metabolism; D012646:Self Administration
D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine