The D2 agonist quinpirole potentiates the discriminative stimulus effects of the D1 agonist SKF 38393.
Although there are two dopamine (DA) receptors (D1 and D2) in the brain, the functional role, particularly of D1 receptors, has remained unclear. Recent research has suggested that D1 and D2 receptors interact synergistically in the generation of certain D2 agonist-induced motor responses. On the other hand, an antagonistic interaction between the receptors has been reported for D1 agonist-induced perioral movements. The purpose of the present experiment was to characterize further the interaction between D1 and D2 receptors using a drug discrimination paradigm, a behavioral paradigm that is sensitive and selective for D1 and D2 agonist and antagonist activity. Rats (N = 8) were trained to discriminate the D1 agonist SKF 38393 (SKF; 10 mg/kg, IP, 30 minutes presession) from saline (1.0 ml/kg, IP, 30 minutes presession) in a 2-lever, food-reinforced-drug discrimination paradigm, SKF (0.2-12.8 mg/kg) produced a dose-related increase in SKF-appropriate responding (maximum 87.5% at 12.8 mg/kg). The D2 agonist quinpirole (QUIN; 0.012-0.1 mg/kg, IP, 10 minutes presession) given alone did not substitute for SKF (maximum 37% SKF-appropriate responding at 0.05 mg/kg). QUIN (0.012 or 0.025 mg/kg) in combination with SKF significantly (p less than 0.05) shifted the SKF dose-response function to the left, suggesting that stimulation of D2 receptors can potentiate a behavioral effect mediated by D1 receptors. Furthermore, when taken together with previous findings that SKF failed to potentiate the discriminative stimulus effects of QUIN, the present results suggest that the nature of D1/D2 receptor interactions depends not only upon the behavior under investigation but also upon the receptor action that the behavior reflects.
Williams
J E
JE
Drug Abuse Research Center, Pritzker School of Medicine, University of Chicago, IL 60637.
Woolverton
W L
WL
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine