Effects of risperidone on phencyclidine-induced behaviors: comparison with haloperidol and ritanserin.
K Kitaichi, K Yamada, T Hasegawa, H Furukawa, Toshitaka Nabeshima
Japanese journal of pharmacology October 1994 DOI: 10.1254/jjp.66.181 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Risperidone Haloperidol Ritanserin Phencyclidine (PCP) |
| Dose | PCP 5 mg/kg i.p. and 10 mg/kg i.p.; risperidone 0.8-2.4 mg/kg p.o.; haloperidol 0.3-1.0 mg/kg p.o.; ritanserin 3-10 mg/kg p.o. |
| Key findings | Risperidone and haloperidol dose-dependently inhibited PCP-induced hyperlocomotion and most stereotyped behaviors in rats, except backpedalling, whereas ritanserin inhibited only head-twitch. Risperidone raised striatal DOPAC and the DOPAC-to-dopamine ratio less than haloperidol. The authors suggest risperidone may act as an antipsychotic via mixed 5-HT2A/D2 antagonism, and that the neurochemical findings may support the view that its extrapyramidal side effects are lower than haloperidol's. |
Abstract
In this study, we investigated whether risperidone, a serotonin-S2A (5-HT2A)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both resperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. 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 suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.