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

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. 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-HT(2A) receptor agonist DOI-induced head twitches as models for positive symptoms of psychosis. 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. 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.