EFFECTS OF RISPERIDONE ON PHENCYCLIDINE-INDUCED BEHAVIORS - COMPARISON WITH HALOPERIDOL AND RITANSERIN

In this study, we investigated whether risperidone, a serotonin-S-2A ( 5-HT2A)/dopamine-D-2 (D-2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol an d ritanserin. Moreover, we also attempted to investigate the effects o f these antipsychotics on the contents of dopamine, serotonin (5-HT) a nd their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, incl uding sniffing, head-weaving, backpedalling and turning. Both risperid one (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibi ted these behaviors, except for backpedalling, in a dose-dependent man ner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped beh aviors, including rearing, sniffing head-twitch, backpedalling and tur ning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3-10 mg/kg, p.o.) inhibited only the head-twitch. These results sugg est that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D-2 ant agonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum w ere lower than those of haloperidol. These findings may support the vi ew that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.