Self-administration of the D1 agonist SKF 82958 is mediated by D1, not D2, receptors.

We have previously reported that two D1 dopamine agonists, SKF 82958 and SKF 77434, are readily self-administered by rats. However, due to the limited selectivities of these agents, it was not possible to attribute their reinforcing effects exclusively to their D1 actions. To assess the relative involvement of D1 and D2 receptors in SKF 82958 reinforcement, rats were pretreated 30 min before self-administration sessions with either the D1-selective antagonist (+)SCH 23390 or the D2-selective antagonist raclopride. The D1 antagonist (+)SCH 23390 (5-20 micrograms/kg, SC) produced significant, dose-related (compensatory) increases in SKF 82958; in contrast, the D2 antagonist raclopride (25-400 micrograms/kg, SC) did not significantly increase SKF 82958 self-administration, although raclopride did increase cocaine self-administration. Compensatory increases in self-administration rates are thought to reflect antagonist-induced reductions in drug reinforcement. Hence, we conclude that SKF 82958 self-administration depends on activation of a D1-regulated reinforcement substrate.