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 D₃-preferring agonists, a D ₂-preferring agonist, and a D₄ agonist. The D ₂-preferring agonist did not maintain responding in any monkeys, and the D₄ agonist was self-administered at low rates, just above those maintained by saline, in one monkey. The D₃-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 D₂-like agonists requires activity at D₃ 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.