Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats.
Author
Summary, in English
n patients with Parkinson's disease, the therapeutic efficacy of L-DOPA medication is gradually lost over time, and abnormal involuntary movements, dyskinesias, gradually emerge as a prominent side-effect in response to previously beneficial doses of the drug. Here we show that dyskinesia induced by chronic L-DOPA treatment in rats with 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway is critically dependent on the integrity and function of the serotonergic system. Removal of the serotonin afferents, or dampening of serotonin neuron activity by 5-HT1A and 5-HT1B agonist drugs, resulted in a near-complete block of the L-DOPA-induced dyskinesias, suggesting that dysregulated dopamine release from serotonin terminals is the prime trigger of dyskinesia in the rat Parkinson's disease model. In animals with complete dopamine lesions, the spared serotonin innervation was unable to sustain the therapeutic effect of L-DOPA, suggesting that dopamine released as a 'false transmitter' from serotonin terminals is detrimental rather than beneficial. The potent synergistic effect of low doses of 5-HT1A and 5-HT1B agonists to suppress dyskinesia, without affecting the anti-parkinsonian effect of L-DOPA in presence of spared dopamine terminals, suggests an early use of these drugs to counteract the development of dyskinesia in Parkinson's disease patients.
Publishing year
2007
Language
English
Pages
1819-1833
Publication/Series
Brain
Volume
130
Issue
7
Links
Document type
Journal article
Publisher
Oxford University Press
Topic
- Neurology
Keywords
- dopamine
- serotonin
- Parkinson's disease
- dyskinesia
- 5-HT1A/1B agonists
Status
Published
Research group
- Neurobiology
- Brain Repair and Imaging in Neural Systems (BRAINS)
ISBN/ISSN/Other
- ISSN: 1460-2156