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 μg/kg, SC) produced significant, dose-related (compensatory) increases in SKF 82958; in contrast, the D₂ antagonist raclopride (25-400 μg/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.