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Tremor in Parkinson's disease and serotonergic dysfunction: an 11C-WAY 100635 PET study
M Doder1, E A Rabiner, N Turjanski
1Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK. m.doder@ic.ac.uk
Neurology
|February 26, 2003
Summary
Parkinson's disease (PD) patients show reduced serotonin 5-HT(1A) receptor binding in the brain's raphe region. This reduction correlates with the severity of parkinsonian tremor, suggesting a role for the serotonergic system in tremor generation.
Area of Science:
- Neuroscience
- Radiology
- Pharmacology
Background:
- Parkinsonian tremor mechanisms are not fully understood.
- Dopaminergic treatment response varies, suggesting non-dopaminergic roles.
- Midbrain raphe 5-HT(1A) receptor binding assesses serotonergic system integrity.
Purpose of the Study:
- To investigate regional cerebral (11)C-WAY 100635 binding to 5-HT(1A) receptors in Parkinson's disease (PD) patients using PET.
- To correlate 5-HT(1A) receptor binding with tremor severity in PD.
Main Methods:
- Positron emission tomography (PET) with (11)C-WAY 100635 was used.
- 23 PD patients and 8 healthy volunteers were studied.
- Compartmental modeling with a cerebellar reference tissue input function calculated binding potential.
Main Results:
- PD patients exhibited a 27% reduction in midbrain raphe 5-HT(1A) binding potential compared to controls (p < 0.001).
- Tremor severity scores (Unified Parkinson's Disease Rating Scale) correlated with raphe 5-HT(1A) binding (p < 0.01).
- Rigidity and bradykinesia did not correlate with this binding.
Conclusions:
- Findings support decreased in vivo serotonergic neurotransmission in PD.
- Reduced raphe 5-HT(1A) binding may reflect receptor dysfunction or Lewy body degeneration.
- Raphe 5-HT(1A) receptor availability is associated with parkinsonian tremor severity.