Behavioral differentiation between effects elicited at dopamine D-1 and D-2 receptors in rats with normosensitive DA...

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.