Effects of dopamine receptor antagonists (D-1 and D-2) on the demand for smoked cocaine base in rhesus monkeys

Rationale: Previous studies suggest that dopamine antagonists may reduce th e reinforcing effects of cocaine. However, the effects of these antagonists on the demand for smoked cocaine base have not been quantified. Objectives : To evaluate the effects of selective D-1 (SCH 23390) and D-2 (raclopride) dopamine receptor antagonists on the demand for smoked cocaine base in rhe sus monkeys using a behavioral economic analysis. Methods: Six rhesus monke ys were trained to self-administer smoked cocaine base (1.0 mg/kg/delivery) under chained fixed-ratio (FR) schedules (FR64, 128, 256, 512, 1024 or 204 8 for lever presses and FR5 for inhalations) during daily 4-h sessions. A m aximum often smoke deliveries were available. After 5 days of stable behavi or at each FR, SCH 23390 (0.01 and 0.056 mg/kg) or raclopride (0.03 and 0.0 56 mg/kg) were injected intramuscularly, before each session, for 3 consecu tive days. Results: Pretreatment with both antagonists dose-dependently red uced cocaine intake across most FR values tested; however, the decrease in consumption was greater at the higher unit prices than at the lower unit pr ices. A statistical estimate of the price (FR) at which maximum responding occurred (P-max) was decreased during drug pretreatment, indicating weakene d reinforcing effectiveness of cocaine. Conclusions: These data suggest tha t both antagonists reduce the reinforcing effectiveness of smoked cocaine b ase, and they have a greater effect on cocaine consumption at higher FR val ues.