Dopamine D(1) antagonist SCH23390 attenuates self-administration of both cocaine and fentanyl in rats.

To investigate the role of dopamine D(1) receptors in the reinforcing effects of cocaine and fentanyl, the effect of the D(1) antagonist SCH23390 on intravenous self-administration of these drugs was investigated in rats using a progressive ratio (PR) reinforcement schedule, during which the rats received the first three injections under an FR1 schedule. Then the number of lever presses required to deliver an injection (lever press ratio) increased by three after every three further injections. The last lever press ratio completed by each rat during each 6 h session was designated the breaking point. Breaking point values increased dose-dependently during both cocaine (0.125-1.00 mg/kg per injection) and fentanyl (0.25-2.00 μg/kg per injection) self-administration. Pretreatment with SCH23390 (0.01 mg/kg, s.c.) decreased breaking point values for both cocaine and fentanyl, reflecting a decrease in the reinforcing efficacy of the drugs. To determine whether the effect of SCH23390 was due to general suppression of the lever pressing response, the effect of SCH23390 (0.01 mg/kg, s.c.) on the performance of rats maintained by water-reinforcement was examined. SCH23390 suppressed performance only transiently, therefore general suppression appears to have little or no effect on the breaking point. These results suggest that dopamine D(1) receptors are involved in mediating the reinforcing effects of both the psychostimulant cocaine and the opiate fentanyl.