Discrepancies in apparent dopamine D2 receptor occupancy between 3H-raclopride and 3H-N-methylspiperone

Competitive inhibition of 3H-raclopride (RAC) and 3H-N-methylspiperone (NMSP) binding against haloperidol, raclopride and NMSP was measured in the mouse striatum. 3H-RAC binding was more sensitive to competitive inhibition by all three compounds compared with 3H-NMSP. For example, 0.3 mg/kg of haloperidol resulted in 95% inhibition of 3H-RAC binding, however only 60% of inhibition of 3H-NMSP binding was found at the same dose of haloperidol. The cross-inhibition experiments using non-radioactive RAC or NMSP as competitors indicated different binding sites for 3H-RAC and 3H-NMSP in mouse striatum. Specifically, about 40% of 3H-NMSP binding was not displaced by treatment with a very high dose of raclopride (3 mg/kg). The time course of inhibition of the specific binding of 3H-RAC and 3H-NMSP were measured following i.p. injection of 0.5 mg/kg of haloperidol. No significant differences in the kinetics of haloperidol inhibition were observed between two radioligands.