Discriminative stimulus properties of D1 and D2 dopamine agonists in rats

Abstract

Rats were trained to discriminate 8.0 mg/kg of SKF 38393 (SKF) or 1.0 mg/kg of piribedil (PIR) from saline. Drugs were given 10 min before each session in a two-lever, food-reinforced (FR 30) drug discrimination paradigm. SKF (2.0-8.0 mg/kg i.p.) produced a dose-related increase in drug-appropriate responding in the SKF group but not in the PIR group. PIR (0.06-1.0 mg/kg i.p.) produced a dose-related increase in drug-appropriate responding in the PIR group but not in the SKF group. Apomorphine (0.03-0.5 mg/kg i.p. also produced a dose-related increase in PIR-appropriate responding, whereas dopamine (DA; 4.0-16 mg/kg i.p.), which does not readily cross the blood-brain barrier, did not. When pretreatment time was varied, SKF-appropriate responding was maximal when 8.0 mg/kg of SKF was injected 30 min before the session. PIR (1.0 mg/kg i.p.) occasioned maximal PIR-appropriate responding when injected 1 or 10 min before the session but did not when injected 30 or 60 min before the session. In rats trained to discriminate SKF (8.0 mg/kg) using a 30-min pretreatment time, the D1 antagonist SCH 23390 blocked the SKF discriminative stimulus (DS) but did not alter the PIR DS in PIR-trained rats. The D2 antagonist pimozide blocked the PIR DS but did not alter the SKF DS. Thus, the DS properties of D1 and D2 agonists are functionally distinct in rats and are antagonized by DA antagonists selective for D1 or D2 receptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)