Antidepressants enhanced the antipsychotic-like effect of aripiprazole in the tests used for evaluaion of some positive and cognitive symptoms of schizophrenia in mice
INTRODUCTION: 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 antipsychotics alleviate not only the positive symptoms of schizophrenia but also the cognitive ones, however those effects are small and the mechanisms of this action are still unknown. A few clinical reports have suggested that antidepressants (ADs) are able to augment the activity of atypical antipsychotics. AIM(S): In the present study, we aimed to evaluate the effect of ADs escitalopram (ESC) or mirtazapine (MIR) and aripiprazole (ARI, an atypical antipsychotic drug) given separately or jointly, on the MK-801-induced positive and cognitive symptoms of schizophrenia in mice. METHOD(S): The experiments were conducted on male Albino Swiss mice (25–27 g). ADs and ARI were given 30 min before MK-801 injection. Locomotor hyperactivity induced by MK-801 (0.3 mg/kg) was measured for 30 min, starting 30 min after MK-801 administration. In the novel object recognition test, MK-801 (0.2 mg/kg) was given 30 min before the first introductory session. Memory retention was evaluated for 5 min, starting 90 min after the introductory session. RESULTS: ARI (0.3 mg/kg) decreased locomotor hyperactivity induced by MK-801 (0.3 mg/kg). Co-treatment with an inactive dose of ARI (0.01 mg/kg) and ESC (5 or 10 mg/kg) or MIR (2.5 and 5 mg/kg) inhibited the effect of MK‑801. Moreover, MK-801 (0.2 mg/kg) decreased the memory retention. ARI (0.3 mg/kg) reversed that effect. Co‑treatment with an inactive dose of ARI (0.03 mg/kg) and ESC (5 and 10 mg/kg) or MIR (2.5 and 5 mg/kg) abolished the deficit of object recognition memory induced by MK-801. CONCLUSIONS: The obtained results suggest that ADs may enhance the antipsychotic‑like effect of ARI in the animal tests used for evaluation of some positive and cognitive symptoms of schizophrenia. FINANCIAL SUPPORT: This study was financially supported by statutory funds of the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.