Self-administration of agonists selective for dopamine D2, D3, and D4 receptors by rhesus monkeys

Mikhail N. Koffarnus, Gregory T. Collins, Kenner C. Rice, Jianyong Chen, James H. Woods, Gail Winger

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalBehavioural pharmacology
Volume23
Issue number4
DOIs
StatePublished - Aug 2012

Keywords

  • D-like agonists
  • reinforcing effects
  • rhesus monkey
  • self-administration

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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