Co-treatment with antidepressants and aripiprazole reversed the MK-801-induced some negative symptoms of schizophrenia in rats.

Abstract

Schizophrenia is a chronic, most devastating psychiatric illness that impairs mental and social functioning. A few clinical reports have suggested that antidepressant drugs are able to augment the activity of atypical antipsychotic drugs, thus effectively improving treatment of some negative symptoms of schizophrenia. The aim of the present study was to investigate the effect of the antidepressant escitalopram or mirtazapine and aripiprazole (an atypical antipsychotic), given separately or jointly, on the deficits induced by MK-801(a noncompetitive N-methyl-d-aspartate receptor antagonist) in the social interaction test in male Sprague-Dawley rats. The social interaction was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. Antidepressants and aripiprazole were given 60 and 30 min before the test, respectively. WAY 100635 (a 5-HT1A antagonist) and SCH 23390 (a dopamine D1 antagonist) were give 20 min before the tests. The present results showed that MK-801 (0.1 mg/kg)-induced deficits in the social interaction test. Aripiprazole (0.1 and 0.3 mg/kg) reversed those effects. Co-treatment with an ineffective dose of aripiprazole (0.03 mg/kg) and escitalopram (5 and 10 mg/kg) or mirtazapine (5 mg/kg) abolished the deficits evoked by MK-801, and those effects were especially blocked by a 5-HT1A receptor antagonist (WAY 100635) or partly by dopamine D1 receptor antagonist (SCH 23390). The obtained results suggest that amelioration of the antipsychotic-like effect of aripiprazole by antidepressants in the MK-801-induced some negative symptoms of schizophrenia in rats may be associated with serotonin 5-HT1A and to a lesser degree with dopamine D1 receptors.