DISCRIMINATIVE STIMULUS PROPERTIES OF COCAINE IN RELATION TO DOPAMINE-D(2) RECEPTOR FUNCTION IN RATS

Previous studies indicate that the discriminative stimulus effects of cocaine are mediated predominantly by indirect activation of dopamine (DA) D2 postsynaptic receptors, although DA D1 receptors may also be i nvolved. In the present study, full or partial D2 agonists and D2 anta gonists were tested for their ability to substitute for, potentiate or antagonize the stimulus effects of cocaine in rats (n = 15) trained t o discriminate cocaine (1 0 mg/kg) from saline in a two-lever, water-r einforced task. The full D2 agonists bromocriptine (1.25-20 mg/kg) and quinpirole (0.013-0.2 mg/kg) engendered substantial cocaine-lever res ponding (>80% drug-lever responding), whereas the partial D2 agonists preclamol (2.5-10 mg/kg) and terguride (0.313-1.25 mg/kg) produced les s than 50% cocaine-lever responding. Co-administration of a threshold dose of cocaine (1.25 mg/kg) with low doses of bromocriptine (1.25-5 m g/kg) or quinpirole (0.025-0.1 mg/kg) induced higher percentages of co caine-lever responding as compared with occasions when these D2 agonis ts were given alone. However, co-administration of this dose of cocain e with preclamol (2.5-10 mg/kg) or terguride (0.313-1.25 mg/kg) did no t alter the percentage of cocaine-lever responding observed when these partial D2 agonists were administered alone. Pretreatment with the D2 antagonists bromuride (0.25-1 mg/kg) and haloperidol (0. 1 25-0.5 mg/ kg) significantly reduced the percentage of cocaine-lever responding. Preclamol (0.625-1 0 mg/kg) and terguride (0.019-5 mg/kg), but not bro mocriptine (2.5-20 mg/kg) or quinpirole (0.01 -0.08 mg/kg), significan tly reduced the percentage of cocaine-lever responding. These results suggest that full D2 agonists substitute completely for cocaine, where as partial D2 agonists do not produce cocaine-like responding. Further more, additive effects amounting to full substitutions (>80% cocaine-l ever responding) are observed only when full, not partial, D2 agonists are combined with a low dose of cocaine. Additionally, partial D2 ago nists antagonize the discriminative stimulus effects of cocaine to an extent similar to that of classical D2 antagonists.