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Licensed Unlicensed Requires Authentication Published by De Gruyter February 11, 2013

The role of serotonin in the antidyskinetic effects of deep brain stimulation: focus on antipsychotic-induced motor symptoms

Meaghan C. Creed and José N. Nobrega


Treatment with the classic antipsychotic drugs (APDs), such as haloperidol (HAL), is associated with both acute and chronic motor side effects. Acutely, these drugs may induce extrapyramidal symptoms, whereas a prolonged treatment may result in tardive dyskinesia (TD). Atypical antipsychotics have a lower incidence of motor side effects, which have been partially ascribed to the antagonism of serotonin (5-HT) receptors. Although there is currently no satisfactory pharmacotherapy for TD, deep brain stimulation (DBS) has emerged as a promising therapy. However, the mechanisms underlying its effects remain largely unknown. DBS has been shown to affect several neurotransmitter systems, including 5-HT. In this review, we outline the involvement of 5-HT in the development of HAL-induced catalepsy and TD. We also discuss the evidence for DBS-induced alterations in 5-HT function and the relevance of serotonergic alterations to the antidyskinetic effects of DBS. The evidence suggests that the serotonergic mechanisms may be involved in the acute and chronic motor side effects of APDs as well as in adverse psychiatric effects that have been reported following DBS. However, the current evidence suggests that 5-HT alterations do not play an important role in the effectiveness of DBS in models of dyskinesias induced by chronic APDs.

Corresponding author: José N. Nobrega, Behavioural Neurobiology Laboratory, Research Imaging Centre, Center for Addiction and Mental Health, 150 College Street, Toronto, Ontario, M5T 1R8 Canada; and Campbell Family Mental Health Research Institute and Departments of Pharmacology and Toxicology, Psychiatry, and Psychology, University of Toronto

Received: 2012-11-21
Accepted: 2012-12-20
Published Online: 2013-02-11
Published in Print: 2013-04-01

©2013 by Walter de Gruyter Berlin Boston

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