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

Behav Pharmacol. 2012 Aug;23(4):331-8. doi: 10.1097/FBP.0b013e3283564dbb.

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 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cocaine / administration & dosage*
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / pharmacology
  • Female
  • Macaca mulatta
  • Male
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D3 / agonists
  • Receptors, Dopamine D4 / agonists
  • Reinforcement Schedule
  • Self Administration

Substances

  • Dopamine Agonists
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Dopamine D4
  • Cocaine