Role of dopamine D1 and D2 receptors in mediating the d-amphetamine discriminative cue.
The role of D1 and D2 dopamine (DA) receptors in mediating the discriminative cue produced by d-amphetamine (0.5 mg/kg) in rats has been assessed by using compounds which exert strong selectivity for each of these DA receptor subtypes. The D2 agonists quinpirole and RU 24213 substituted completely for d-amphetamine, while the D1 agonists SKF 38393 and SKF 81297 failed to exert such effects. On the other hand, the D2 antagonists raclopride and YM 09151-2, and D1 antagonists SCH 23390 and SKF 83566, all completely blocked d-amphetamine discrimination. The D2 antagonists produced more pronounced inhibitory effects on response rate than did D1 antagonists. Quinpirole substitution for d-amphetamine was blocked by YM 09151-2, but not by SCH 23390, while the locomotor stimulatory effect of quinpirole was inhibited by both drugs. The present findings confirm that D2 receptors play a primary role in the d-amphetamine discriminative cue, while the precise role of D1 receptors remains to be disclosed.
Neuropsychopharmacology Laboratory, Department of Psychology, University of Reading, U.K.
L J
LJ
Furmidge
M
M
Exner
D
D
Clark
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003463:Cues; D003913:Dextroamphetamine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012055:Reinforcement Schedule
D014150:Antipsychotic Agents; D001549:Benzamides; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; C030265:nemonapride; D003913:Dextroamphetamine; D004298:Dopamine