Changes in 5-HT2A Receptor Expression in Untreated, de novo Patients with Parkinson's Disease

Background: Serotonin (5-HT) has long been implied in the pathophysiology of Parkinson's disease (PD). In addition, the 5-HT2A receptor is associated with the regulation of motor function and mood. Objective: To assess regional 5-HT2A receptor expression in unmedicated patients with de novo PD. Methods: Eight de novo, drug naive patients with PD and eight healthy control subjects underwent a single photon emission computed tomography (SPECT) scan with the highly selective 5-HT2A radioligand I-123-5-I-R91150. Results: In de novo PD patients 5-HT2A receptor binding was significantly reduced in the anterior striatum and the premotor cortex in PD patients compared to controls. In addition, occipital binding was elevated in PD patients. No changes in 5-HT2A receptor binding were found in the prefrontal and parietal cortex. Conclusion: In de novo PD patients, 5-HT2A receptor expression is changed in key areas of the basal ganglia-thalamocortical motor circuit and occipital cortex. This suggests altered 5-HT neurotransmission to contribute to development of PD motor and non-motor symptoms.