Effect of co-treatment with mirtazapine and risperidone in animal models of the positive symptoms of schizophrenia in mice

摘要

Background: Several clinical reports have suggested that the mirtazapine-induced augmentation of risperidone activity may effectively improve the positive, negative and some cognitive symptoms of schizophrenia. Methods: The present study was aimed at examining the effect of mirtazapine and risperidone, given separately or jointly in mice, on the locomotor hyperactivity induced by D-amphetamine or MK-801 as well as a 5-HT2A receptor agonist DOI-induced head twitches as models for positive symptoms of psychosis. Results: The obtained results showed that co-treatment with mirtazapine (2.5 or 5 mg/kg) and risperidone (0.01 mg/kg) inhibited the locomotor hyperactivity induced by D-amphetamine or MK-801. Moreover, co-administration of mirtazapine (1.25 or 2.5 mg/kg) and risperidone (0.01 mg/kg) reduced the number of head twitches induced by DOI, whereas those drugs given separately changed neither the locomotor hyperactivity induced by D-amphetamine or MK-801 nor the syndrome induced by DOI. Conclusion: The obtained results indicated that lower doses of mirtazapine enhanced the antipsychotic-like effect of risperidone in animal tests of positive symptoms of schizophrenia. Further studies are necessary to elucidate its mechanism of action.