Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D-2 and serotonin 5-HT2A receptors in the rat brain

The effects of 3-week treatment with a typical antipsychotic drug chlorprom azine and three atypical antipsychotic drugs (risperidone, olanzapine and p erospirone) on the binding to dopamine D-2 and serotonin 5-HT2A receptors w ere examined in the rat stratum and frontal cortex, respectively. Subchroni c treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) signif icantly increased D-2 receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.2 5, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week adminis tration of chlorpromazine (5, 10 mg/kg) and olanzapine (1, 2 mg/kg) signifi cantly decreased 5-HT2A receptors, but risperidone (0.25, 0.5 mg/kg) or per ospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occu pation for D-2 and 5-HT2A receptors using N-ethoxycarbonyl-2-ethoxy-1,2-dih ydroquinoline (EEDQ)) suggested that high occupation of 5-HT2A receptors wi th lower D-2 receptor occupancy might be involved in the absence of up-regu lation of D-2 receptors after subchronic treatment with some atypical antip sychotic drugs.