Behavioral differentiation between effects elicited at dopamine D-1 and D-2 receptors in rats with normosensitive DA receptors.
The interaction between D-1 and D-2 receptor agonists was investigated in three behavioral test models. In two models (circling behavior in rats with hemitransection; stereotyped behavior in naive rats) an enabling role of D-1 receptor agonists in expressing the effect of D-2 agonists was found: D-1 agonists alone were ineffective, D-2 agonists had low maximum effects, whereas the combination induced marked activity. Consistent with this, the effect of combined D-1/D-2 receptor stimulation was antagonized either by D-1 or D-2 antagonists. In contrast, the effect of D-1 and D-2 agonists and antagonists were differentiated in drug discrimination studies, using the cue induced by the D-1 agonist SK & F 38393 or by the D-2 agonist (-)-NPA versus saline. The results thus indicate a functional relevance of D-1 receptors and show that the coupling between D-1 and D-2 receptors critically depends on the specific behavior under study.
Arnt
J
J
Department of Pharmacology, H. Lundbeck A/S, Copenhagen-Valby, Denmark.
Hyttel
J
J
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013239:Stereotyped Behavior / Q000187:drug effects
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001058:Apomorphine