Jan 9, 2007

5-HT6 receptor antagonist SB-399885 potentiates haloperidol and risperidone-induced dopamine efflux in the medial prefrontal cortex or hippocampus

Brain Research
Zhu LiHerbert Y Meltzer

Abstract

Many studies suggest that the 5-HT6 receptors are involved, along with other 5-HT receptors, in the pathophysiology and pharmacotherapy of schizophrenia. It is a putative therapeutic target of atypical antipsychotic drugs, notably clozapine, as well as some other psychotropic agents. Preferential potentiation of dopamine (DA) efflux in the medial prefrontal cortex (mPFC) and hippocampus (HIP) has been suggested to contribute to the ability of atypical antipsychotic drugs (APDs), e.g. clozapine, risperidone, olanzapine and ziprasidone, to improve cognitive function in schizophrenia. The present study demonstrated that SB-399885, a selective 5-HT6 receptor antagonist, at doses of 3 and 10 mg/kg, had no effect on cortical DA release in freely moving rats. However, both doses of SB-399885 slightly but significantly increased DA release in the HIP. Of particular interest, SB-399885, 3 mg/kg, significantly potentiated the ability of a typical antipsychotic drug haloperidol, a D2 receptor antagonist, at a dose of 0.1 mg/kg, to increase DA release in the HIP but not the mPFC. The atypical antipsychotic drug risperidone, a multireceptor antagonist, which lacks 5-HT6 receptor antagonist properties, at doses of 0.1, 0.3 and 1.0 mg/kg, pro...Continue Reading

Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Dialysis Solutions
Atypical Antipsychotic [EPC]
Receptor, Serotonin,5-HT2A
Amphetamine
Cortex Bone Disorders
Adrenal Cortex Diseases
Assay OF Haloperidol
Olanzapine
Prefrontal Cortex

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