Self-administration of agonists selective for dopamine D2, D3, and D4 receptors by rhesus monkeys.
Dopamine receptor mechanisms are believed to play a role in the reinforcing effects of cocaine and other drugs of abuse. The lack of receptor-selective agonists has made it difficult to determine the role of the individual dopamine receptors in mediating these reinforcing effects. In this study, rhesus monkeys with a history of intravenous cocaine self-administration were tested for the reinforcing effects of several D(3)-preferring agonists, a D(2)-preferring agonist, and a D(4) agonist. The D(2)-preferring agonist did not maintain responding in any monkeys, and the D(4) agonist was self-administered at low rates, just above those maintained by saline, in one monkey. The D(3)-preferring agonists were self-administered by approximately half of the animals, although at lower rates than cocaine. These results indicate that the apparent limited reinforcing effectiveness of D(2)-like agonists requires activity at D(3) receptors. Previous data from this laboratory and others also suggest that these drugs may not serve as reinforcers directly; the behavior may be maintained by response-contingent delivery of stimuli previously paired with cocaine. The ability of drug-related stimuli to maintain responding apparently differs among monkeys and other organisms, and may be related to individual differences in drug-taking behavior in humans.
Virginia Tech Carilion Research Institute, Roanoke, 24016, USA. mickyk@vt.edu
Mikhail N
MN
Koffarnus
Gregory T
GT
Collins
Kenner C
KC
Rice
Jianyong
J
Chen
James H
JH
Woods
Gail
G
Winger
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists; D050638:Receptors, Dopamine D4 / Q000819:agonists; D012055:Reinforcement Schedule; D012646:Self Administration
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D003042:Cocaine