Atypical antipsychotic effects of quetiapine fumarate in animal models

AIM: To evaluate the effect of quetiapine fumarate in animal models of schi zophrenia and its possibility to induce extrapyramidal side effects(EPSE). METHODS: The enhancement of immobility in a forced swimming test of mice in duced by repeated treatment with phencyclidine and amphetamine swimming "no rmalization" test of mice were used as animal models of negative and positi ve symptoms of schizophrenia, respectively. The paw test of rats was used t o evaluate the possibility by quetiapine fumarate to induce EPSE. RESULTS: After treatment with phencyclidine (10 mg.kg(-1).d(-1), sc, 14 d), the immo bility time in the forced swimming test of mice was increased (P < 0.01). Q uetiapine fumarate (20, 40, and 80 mg.kg(-1), ig) and clozapine (10 and 30 mg.kg(-1), ig) attenuated the enhanced immobility an the forced swimming te st induced by repeated treatment with phencyclidine ( P < 0.01), whereas ha loperidol (0.3 and 1 mg.kg(-1), ig) had no effect. In amphetamine swimming "normalization" test, quetiapine fumarate ameliorated the disorder induced by amphetamine in a dose-dependent manner. In paw test, quetiapine fumarate was much less effective in increasing the forelimb retraction time (FRT) t han the hindlimb retraction time (HRT). The minimal effective dose (MED) of HRT (MEDHRT) and FRT (MEDFRT) Of quetiapine fumarate was 20 mg kg(-1) and 100 mg.kg(-1), respectively, and the ratio of MEDFRT to MEDHRT was 5. CONCL USION: The effects of quetiapine fumarate in these models indicated its cli nical effect on schizophrenia with a reduced liability to produce EPSE.