Evaluation of anti-psychotic effect of nimodipine using methylphenidate as a model to induce psychosis in albino mice

Abstract

Background: Schizophrenia is a functional psychotic disorder currently treated by typical and atypical antipsychotic drugs. A large group of patients remain resistant to therapy. Nimodipine has been found effective for treating resistant bipolar mood disorder which is linked genetically with schizophrenia and has a high overlap of neurotransmitters in the etiopathology. Previous studies to evaluate nimodipine’s antipsychotic activity have shown inconsistent results. Methylphenidate, a CNS stimulant like amphetamine, has been shown to induce stereotypy in animals and can be proposed as an alternative model for psychosis. Methods: Methylphenidate 5 mg/kg was given intraperitoneally to induce psychosis in swiss albino mice (n=6). Nimodipine was given alone in doses of 2.5 and 5 mg/kg by i.p route and in combination with haloperidol 0.1 mg/kg and effects were compared with haloperidol 0.2mg/kg. Activity of nimodipine was also assessed on the haloperidol induced catalepsy test. Statistical analysis was done with ANOVA followed by Bonferroni’s test using SPSS v. 20.0. Results: Methylphenidate successfully induced characteristic stereotypy behaviour in mice similar to amphetamine. Both nimodipine 5 mg/kg and haloperidol 0.2 mg/kg showed significant reduction in stereotypy behaviour with no statistical difference between the two; result with nimodipine were only slightly inferior to haloperidol. Nimodipine 5 mg/kg with haloperidol 0.1 mg/kg showed significantly better activity than haloperidol in standard dose of 0.2 mg/kg. Nimodipine did not show significant activity on the haloperidol induced catalepsy test. Conclusions: Methylphenidate has potential to be used as an alternative model for inducing psychosis in animals and nimodipine shows promising results for use as adjuvant antipsychotic drug.