The effect of combined treatment with escitalopram and risperidone on the MK-801-induced changes in the object recognition test in mice

Background: Atypical antipsychotic drugs have some efficacy in alleviating the negative and some cognitive symptoms of schizophrenia but those effects are small and mechanisms of this action are still unknown. A few clinical reports have suggested that the antidepressant drugs, especially selective serotonin reuptake inhibitors (SSRI) are able to augment the activity of atypical antipsychotic drugs, thus effectively improving treatment of the negative and some cognitive symptoms of schizophrenia. Methods: In the present study, we evaluated the effect of escitalopram (SSRI) and risperidone (an atypical antipsychotic drug), given separately or jointly, on the effect of MK-801 (a NMDA receptor antagonist) given before to the first introductory session, in the object recognition memory test. The mice were tested for the ability to discriminate between an old, familiar and a novel object. Escitalopram and risperidone were given 30 min before MK-801, and MK-801 was administered 30 min before the first introductory session. Memory retention was evaluated 90 min after the introductory session. Results: The obtained results showed that MK-801 (0.2 mg/kg) decreased memory retention when given before the introductory session. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and escitalopram (5 or 10 mg/kg) abolished the deficit of object recognition memory induced by MK-801. Conclusions: The obtained results suggest that escitalopram may enhance the antipsychotic-like effect of risperidone in the animal tests used for evaluation of some cognitive symptoms of schizophrenia. (c) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.