Improving the Treatment of Schizophrenia: Role of 5-HT Receptors in Modulating Cognitive and Extrapyramidal Motor Functions
2013
Patients with schizophrenia exhibit various clinical symptoms including positive and negative symptoms,
neurocognitive impairments and mood disturbances. Although a series of second generation antipsychotics (SGAs) (e.g.,
risperidone, olanzapine and quetiapine) have been developed in the past two decades, clinical reports do not necessarily
show advantages over first generation antipsychotics (FGAs) in the treatment of schizophrenia, especially in their efficacy
against cognitive impairment and ability to cause extrapyramidal side effects (EPS). Recently, several lines of studies
have revealed therapeutic roles of 5-HT receptors in modulating cognitive impairments and extrapyramidal motor
disorders. Specifically, inhibition of 5-HT 1A , 5-HT 3 and 5-HT 6 receptors or activation of 5-HT 4 receptors alleviates
cognitive impairments (e.g., deficits in learning and memory). In addition, stimulation of 5-HT 1A receptors or inhibition of
5-HT 3 and 5-HT 6 receptors as well as 5-HT 2A/2C receptors can ameliorate extrapyramidal motor disorders. Thus,
controlling the activity of 5-HT 1A , 5-HT 3 or 5-HT 6 receptors seems to provide benefits by both alleviating cognitive
impairments and reducing antipsychotic-induced EPS. This article reviews the functional roles and mechanisms of 5-HT
receptors in the treatment of schizophrenia, focusing on the serotonergic modulation of cognitive and extrapyramidal
motor functions, and illustrates future therapeutic strategies.
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