Differential effects of dopamine receptor subtype-specific agonists with respect to operant behavior maintained on a differential reinforcement of low-rate responding (DRL) schedule

Pharmacol Biochem Behav. 2015 Mar;130:67-76. doi: 10.1016/j.pbb.2015.01.002. Epub 2015 Jan 10.


Previous studies have shown that d-amphetamine, a dopamine (DA) indirect agonist, alters operant responding with respect to the behavior maintained on a differential reinforcement of low-rate (DRL) schedule of reinforcement. These behavioral changes have been presumed to result from drug-induced hyperdopaminergia that leads to activation of DA receptors. This study investigated the acute dose effects of DA receptor subtype-selective agonists on the performance of DRL 10-sec behavior by rats. SKF38393 (a D1 receptor agonist) and quinpirole (a D2/D3 receptor agonist) were able to dose-dependently disrupt DRL 10-sec behavior by decreasing the total responses, the non-reinforced responses, and the peak rate of response. Bromocriptine (a D2/D3 receptor agonist) produced a significantly different pattern of behavioral changes when examined during two distinct time phases (15 min and 3 hr after the drug injection). DRL responding was only altered at higher doses of bromocriptine in the second phase as indicated by decreasing reinforced responses and peak rate, together with an increase of burst responses. In contrast to the D1 and D2/D3 receptor agonists, PD168077 (a D4 receptor agonist) did not affect DRL 10-sec behavior. None of these tested drugs affected DRL 10-sec behavior in a manner similar to that of d-amphetamine. These findings show that there are differential effects on the performance of DRL 10-sec behavior when drugs are able to preferentially activate D1, D2/D3 and D4 receptors, supporting the assertion that there is functional heterogeneity of the DA receptor subtypes.

Keywords: Bromocriptine; Operant psychopharmacology; PD168077; Quinpirole; SKF38393.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology*
  • Animals
  • Benzamides / pharmacology*
  • Bromocriptine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Piperazines / pharmacology*
  • Quinpirole / pharmacology*
  • Rats
  • Reinforcement Schedule*
  • Time Factors


  • Benzamides
  • Dopamine Agonists
  • N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide
  • Piperazines
  • Quinpirole
  • Bromocriptine
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine