The D1 dopamine agonist SKF 38393 functions as a discriminative stimulus in rats

Rats (N = 11) were trained to discriminate SKF 38393 (8.0 mg/kg, IP), a D1 dopamine receptor agonist, from saline in a two-lever, food-reinforced (FR 30) drug discrimination paradigm. The discrimination was acquired by nine rats within an average of 77 +/- 6 (SEM) sessions. Subsequently, various doses of SKF 38393 as well as SKF 82526, a potent, selective D1 agonist that does not readily penetrate the blood-brain barrier, were injected prior to test sessions. SKF 38393 (2-16 mg/kg) produced a dose-related increase in the percent of responses that occurred on the drug lever during test sessions. On the other hand, SKF 82526 (0.125 and 1.0 mg/kg) induced no drug-appropriate responding. This experiment establishes that SKF 38393 can serve as a discriminative stimulus in rats. Furthermore, the observation that SKF 82526 did not substitute for SKF 38393 in this paradigm makes it unlikely that this effect involves a peripheral site of action. The results suggest the existence of a functional, behaviorally relevant D1 dopamine receptor in the CNS of rats.