Effects of dopamine receptor antagonists (D₁ and D₂) on the demand for smoked cocaine base in rhesus monkeys

Rationale: Previous studies suggest that dopamine antagonists may reduce the 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 D₁ (SCH23390) and D₂ (raclopride) dopamine receptor antagonists on the demand for smoked cocaine base in rhesus monkeys using a behavioral economic analysis. Methods: Six rhesus monkeys 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 2048 for lever presses and FR5 for inhalations) during daily 4-h sessions. A maximum of ten smoke deliveries were available. After 5 days of stable behavior at each FR, SCH 23390 (0.01 and 0.056 mg/kg) or raclopride (0.03 and 0.056 mg/kg) were injected intramuscularly, before each session, for 3 consecutive days. Results: Pretreatment with both antagonists dose- dependently reduced cocaine intake across most FR values tested; however, the decrease in consumption was greater at the higher unit prices that at the unit prices. A statistical estimate of the price (FR) at which maximum responding occurred (P(max)) was decreased during drug pretreatment, indicating weakend reinforcing effectiveness of cocaine. Conclusions: These data suggest that both antagonists reduce the reinforcing effectiveness of smoked cocaine base, and they have a greater effect on cocaine consumption at higher FR values.