The effect of chronic co-treatment with risperidone and novel antidepressant drugs on the dopamine and serotonin levels in the rats frontal cortex.

Abstract

Preclinical and clinical studies have suggested a beneficial effect of combination treatment with atypical antipsychotic drugs and antidepressants (ADs) in schizophrenia and in drug-resistant depression. In the present study, we investigated the effect of chronic administration of risperidone and ADs (escitalopram or mirtazapine), given separately or jointly on the extracellular levels of dopamine (DA) and serotonin (5-HT) in the rat frontal cortex. The animals were administered risperidone (0.2mg/kg) and escitalopram (5mg/kg) or mirtazapine (10mg/kg) repeatedly for 14days. The release of monoamines in the rat frontal cortex was evaluated using a microdialysis, and DA and 5-HT levels were assayed by HPLC. We also measured the locomotor activity, catalepsy and recognition memory in these rats. Chronic risperidone treatment (0.2mg/kg) increased the extracellular levels of DA and 5-HT. Co-treatment with risperidone and escitalopram (5mg/kg) or mirtazapine (10mg/kg) more efficiently increased the release of 5-HT but not DA in the rat frontal cortex, as compared to drugs given alone. Moreover, risperidone, escitalopram and mirtazapine given alone or in combination significantly decreased the locomotor activity and only mirtazapine increased the catalepsy evoked by risperidone. Combined treatment with risperidone and ADs impaired recognition memory in these rats. The obtained results suggest that chronic co-administration of risperidone and escitalopram or mirtazapine more efficiently increased 5-HT release in the rat frontal cortex as compared to drugs given alone and suggest that this effect may be of importance to the pharmacotherapy of schizophrenia and drug-resistant depression.