Effect of combined treatment with aripiprazole and antidepressants on the MK-801-induced deficits in recognition memory in novel recognition test and on the release of monoamines in the rat frontal cortex.

According to preclinical and clinical studies, the antidepressant-induced increase in the activity of atypical antipsychotics may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. In the present study, we aimed to evaluate the effects of the antidepressants escitalopram and mirtazapine and the atypical antipsychotic drug aripiprazole, administered separately or in combination, on the MK-801-induced deficits in the recognition memory test and on the extracellular levels of monoamines and their metabolites in the rat frontal cortex. Based on the results of the behavioral tests, co-treatment with an ineffective dose of aripiprazole (0.1 mg/kg) and escitalopram (2.5 and 5 mg/kg) or mirtazapine (5 mg/kg) abolished the deficits evoked by MK-801 in the novel object recognition test, and those effects were blocked by the 5-HT1A receptor antagonist (WAY 100635) or the dopamine D1 receptor antagonist (SCH 23390). Moreover, co-treatment with aripiprazole (0.3 mg/kg) and escitalopram (5 mg/kg) significantly increased the levels of noradrenaline and serotonin, decreased the level of its metabolite, and did not alter level of dopamine, but decreased the levels of its metabolites. In addition, co-treatment with aripiprazole (0.3 mg/kg) and mirtazapine (10 mg/kg) significantly increased the level of noradrenaline, did not change the levels of dopamine and serotonin, but increased the levels of their metabolites. Based on these results, the increase in the extracellular levels of noradrenaline or serotonin in the cortex induced by co-treatment with an antidepressant and aripiprazole may be very important for the pharmacotherapy of negative and some cognitive symptoms of schizophrenia.