Background: Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms often accompanied by depression and cognitive deficits. Positive symptoms, like delusions and hallucinations are caused by an excess of dopamine (DA) signaling and are treated with the second generation antipsychotic drugs. Negative symptoms of schizophrenia are represented by social withdrawal, apathy and blunted emotional response. It was demonstrated that co-administration of risperidone and selective serotonin reuptake inhibitors alleviated depressive symptoms and cognitive dysfunction in animal models of schizophrenia. Moreover, combination of fluoxetine or mirtazapine with risperidone increased DA and 5-hydroxytryptamine (5-HT) release in the rat frontal cortex more potently than either drug given separately. The present study aimed to investigate whether combination of risperidone and escitalopram is effective in increasing DA and 5-HT release.
Methods: The extracellular level of neurotransmitters in the rat frontal cortex and nucleus accumbens was examined using microdialysis in freely moving animals. The dialysate concentration of DA and 5-HT was assayed by HPLC.
Results: It was found that risperidone (0.2 and 1mg/kg) and escitalopram (5 and 10mg/kg) given together significantly increased cortical DA and 5-HT levels and were more efficient in enhancing neurotransmitter concentrations than any single-drug treatment. A similar effect on DA and 5-HT release was observed in the nucleus accumbens after administration of risperidone (1mg/kg) and escitalopram (5mg/kg).
Conclusions: The present study demonstrates that co-administration of risperidone and escitalopram may be used to treat positive and negative symptoms of schizophrenia and will allow to minimize the drugs' side effects.
Keywords: Dopamine; Frontal cortex; In vivo microdialysis; Nucleus accumbens; Serotonin.
Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.