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

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. copyright © 2012 by institute of pharmacology polish academy of sciences.