THE D1 AGONISTS SKF-82958 AND SKF-77434 ARE SELF-ADMINISTERED BY RATS

The reported failure of the prototypical (but partial) D1 agonist SKF 38393 to support self-administration behavior contradicts hypotheses of D1-mediated reinforcement. Here we demonstrate that rats will readily self-administer two SKF 38393 analogs, the partial D1 agonist SKF 77434 and the full D1 agonist SKF 82958; both compounds produce inverted U-shaped dose-response curves. When compared to the parent compound, both analogs display enhanced lipophilicity and somewhat decreased D1/D2 selectivity. It is suggested that these properties, rather than partial D1 agonist efficacy, explain the failure of SKF 38393 to act as a reinforcer.