Title : Co-treatment with antidepressants and aripiprazole reversed the MK-801-induced schizophrenia-like behavior in rats
Abstract:
Schizophrenia is a devastating psychiatric disorder that impairs mental and social functioning and affects approximately 1% of the world’s population. It is known that in contrast to pharmacotherapy with typical antipsychotics, atypical antipsychotic agents alleviate not only the positive symptoms of schizophrenia but also the negative ones, but those effects are small and mechanisms of this action are still unknown. A few clinical reports have suggested that antidepressant drugs are able to augment the activity of atypical antipsychotic drugs, thus effectively improving treatment of the negative and some cognitive symptoms of schizophrenia. Thus, the aim of the present study was to investigate the effect of 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 and in novel object recognition tests in male Sprague-Dawley rats. The social interaction was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg, sc) administration. In the novel object recognition test rats were tested for the ability to discriminate between an old, familiar and a novel object. Antidepressants and aripiprazole were given 30 min before MK-801, and MK-801 (0.1 mg/kg, ip) was administered 30 min before the first introductory session. Memory retention was evaluated for 5 min, starting 60 min after the introductory session. WAY 100635 (a 5-HT1A antagonist, 0.1 mg/kg, sc) and SCH 23390 (a dopamine D1 antagonist, 0.25 mg/kg, ip) 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 and decreased memory retention in the novel recognition test. Aripiprazole (0.3 mg/kg) reversed those effects. Co-treatment with an ineffective dose of aripiprazole (0.03 mg/kg) and escitalopram and mirtazapine (5 mg/kg, ip) abolished the deficits evoked by MK-801, and those effects were partly blocked by a 5-HT1A receptor antagonist (WAY 100635) or a dopamine D1 receptor antagonist (SCH 23390). The obtained results suggest that ameliorate the antipsychotic-like effects of aripiprazole by antidepressants in the MK-801-induced deficits in the social interaction and memory retention may associated with serotonin 5-HT1A and dopamine D1 receptors.
