Role of Serotonin Neurons in L-DOPA- and Graft-Induced Dyskinesia in a Rat Model of Parkinson's Disease:
http://www.hindawi.com/journals/pd/2012/370190/
Review Article
Role of Serotonin Neurons in L-DOPA- and Graft-Induced Dyskinesia in a Rat Model of Parkinson's Disease
Eunju Shin,1 Elisabetta Tronci,2 and Manolo Carta2
1Division of Neurobiology, Wallenberg Neuroscience Center, Lund University, 221 84 Lund, Sweden
2Department of Biomedical Science, Cagliari University, Cittadella Universitaria, SS 554 km 4.500, 09042 Monserrato, Italy

Received 16 February 2012; Revised 2 April 2012; Accepted 10 April 2012

Academic Editor: Gilberto Fisone

Copyright © 2012 Eunju Shin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

L-DOPA, the most effective drug to treat motor symptoms of Parkinson's disease, causes abnormal involuntary movements, limiting its use in advanced stages of the disease. An increasing body of evidence points to the serotonin system as a key player in the appearance of L-DOPA-induced dyskinesia (LID). In fact, exogenously administered L-DOPA can be taken up by serotonin neurons, converted to dopamine and released as a false transmitter, contributing to pulsatile stimulation of striatal dopamine receptors. Accordingly, destruction of serotonin fibers or silencing serotonin neurons by serotonin agonists could counteract LID in animal models. Recent clinical work has also shown that serotonin neurons are present in the caudate/putamen of patients grafted with embryonic ventral mesencephalic cells, producing intense serotonin hyperinnervation. These patients experience graft-induced dyskinesia (GID), a type of dyskinesia phenotypically similar to the one induced by L-DOPA but independent from its administration. Interestingly, the 5-HT1A receptor agonist buspirone has been shown to suppress GID in these patients, suggesting that serotonin neurons might be involved in the etiology of GID as for LID. In this paper we will discuss the experimental and clinical evidence supporting the involvement of the serotonin system in both LID and GID.