Modulation of cocaine's discriminative stimulus effects by dopamine D(1) agonists in rhesus monkeys

Pharmacol Biochem Behav. 2001 Feb;68(2):301-9. doi: 10.1016/s0091-3057(00)00462-7.

Abstract

Dopamine (DA) D(1) agonists are classified as high- or low-efficacy on the basis of in vitro functional measures as compared to DA. In monkeys self-administering cocaine, high-efficacy D(1) agonists have been shown to have reinforcing effects, while low-efficacy agonists do not. However, the relationship between D(1) agonist efficacy and cocaine-like discriminative stimulus effects, particularly in rhesus monkeys, is not clear. The present study investigated the discriminative stimulus effects of a high- (SKF 81297) and a low-efficacy (SKF 38393) D(1) agonist in rhesus monkeys (n=4) trained to discriminate cocaine from saline using a two-lever drug discrimination procedure. In a second experiment, the effects of agonist pretreatments, as well as pretreatment with a D(1) antagonist, on cocaine's discriminative stimulus effects were evaluated. SKF 81297 (0.01-1.7 mg/kg) fully substituted for cocaine in three of four animals (> 80% cocaine-appropriate responding), while SKF 38393 (0.3-10 mg/kg) occasioned < 50% cocaine-appropriate responding in all subjects. When given as a pretreatment, neither agonist altered cocaine's discriminative stimulus effects at the doses tested. In contrast, the D(1) antagonist SCH 23390 attenuated cocaine's discriminative stimulus effects. These results indicate that D(1) agonists have cocaine-like discriminative stimulus effects in rhesus monkeys that are consistent with their in vitro efficacies. However, when given in combination with cocaine, D(1) agonist efficacy does not appear to be a major factor in modifying cocaine's discriminative stimulus effects.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology*
  • Animals
  • Benzazepines / pharmacology*
  • Cocaine / pharmacology*
  • Discrimination Learning / drug effects*
  • Discrimination Learning / physiology
  • Dopamine Agonists / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Macaca mulatta
  • Male
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Dopamine D1 / physiology

Substances

  • Benzazepines
  • Dopamine Agonists
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • SK&F 81297
  • Cocaine