Effects of selective dopamine receptor agonists in rats trained to discriminate apomorphine from saline

Abstract

Rats (N=12) were trained to discriminate apomorphine (0.25 mg/kg, IP) from saline in a two-lever, food-reinforced (FR 30) drug discrimination paradigm. When the discrimination was acquired, various doses of apomorphine as well as several other dopamine receptor agonists were injected before test sessions. Apomorphine (0.03–0.25 mg/kg, IP) produced a dose-related increase in the percent of responses that occurred on the drug lever during test sessions. The selective DA 2 receptor agonist piribedil (0.25–8.0 mg/kg, IP) produced a dose-related increase in drug lever responding that was similar to that seen with apomorphine. On the other hand, administration of the selective DA 1 receptor agonist SKF 38393 (1.0–32 mg/kg, IP) resulted in principally saline lever responding, even at doses that substantially reduced the rate of responding. Administration of dopamine (1.0–8.0 mg/kg, IP), which does not readily cross the blood-brain barrier, also resulted in principally saline lever responding. These results suggest that the discriminative stimulus properties of apomorphine are based on its action at a receptor that is similar to the DA 2 receptor that has been characterized in the periphery and that this receptor is centrally located.