ABSTRACT
Title
Role of serotonin system in the appearance of L-DOPA- and graft-induced dyskinesias
Authors
E. Shin1, A. Björklund1, M. Carta1,2
1Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University
2 Department of Neuroscience, Cagliari University
1Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University
2 Department of Neuroscience, Cagliari University
Abstract
In recent years, the serotonin system has emerged as an interesting player contributing to the appearance of L-DOPA-induced dyskinesia (LID) in Parkinson´s disease. In fact, we have shown that removal of the serotonin innervation by toxin lesion, or silencing of serotonin neuron activity by 5-HT1A/1B receptor agonists suppress already established dyskinesia and prevent its development in the rat and monkey models of Parkinson´s disease. The discovery of a potent synergistic effect in the anti-dyskinetic efficacy of 5-HT1A and 5-HT1B receptor agonists has encouraged clinical application of these findings. Indeed, a double-blind, proof-of-concept clinical trial is now on-going in a small number of patients the test the feasibility of the above pharmacological approach to treat dyskinesia.
Transplantation of embryonic dopamine cells is a therapeutic approach to Parkinson´s disease that has been tested in clinical trials with variable results. Appearance of the so-called graft-induced dyskinesia (GID) in a subset of grafted patients (which is independent from administration of L-DOPA) has contributed to prevent further investigation of this therapeutic approach. In light of the emerging role of the serotonin system in the appearance of LID and of the recent finding of the presence of an intense serotonin hyperinnervation in grafted patients, it has been raised the possibility that the serotonin system may play a role also in this form of abnormal involuntary movements. Indeed, the partial 5-HT1A agonist buspirone has been shown to suppress GID in a small group of grafted patients. We are now investigating the involvement of the serotonin system in the appearance of GID in the rat model, where dyskinesias are induced in grafted emi-parkinsonian animals upon administration of low amphetamine doses. Results will be presented at the meeting.
Transplantation of embryonic dopamine cells is a therapeutic approach to Parkinson´s disease that has been tested in clinical trials with variable results. Appearance of the so-called graft-induced dyskinesia (GID) in a subset of grafted patients (which is independent from administration of L-DOPA) has contributed to prevent further investigation of this therapeutic approach. In light of the emerging role of the serotonin system in the appearance of LID and of the recent finding of the presence of an intense serotonin hyperinnervation in grafted patients, it has been raised the possibility that the serotonin system may play a role also in this form of abnormal involuntary movements. Indeed, the partial 5-HT1A agonist buspirone has been shown to suppress GID in a small group of grafted patients. We are now investigating the involvement of the serotonin system in the appearance of GID in the rat model, where dyskinesias are induced in grafted emi-parkinsonian animals upon administration of low amphetamine doses. Results will be presented at the meeting.