Downregulation of Striatal Dopamine D2 Receptors in Advanced Parkinson’s Disease Contributes to the Development of Motor Fluctuation

• Published in: European neurology Vol. 47; no. 2; pp. 113 - 117
• Main Authors: Hwang, Wen-Juh, Yao, Wei-Jen, Wey, Shiaw-Pyng, Shen, Lie-Hang, Ting, Gann
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2002; S. Karger AG
• Subjects: Adult; Aged; Benzamides; Biological and medical sciences; Corpus Striatum - diagnostic imaging; Corpus Striatum - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Iodine Radioisotopes; Levodopa - adverse effects; Levodopa - therapeutic use; Male; Medical sciences; Middle Aged; Motor Skills - drug effects; Neurologic Examination - drug effects; Neurology; Original Paper; Parkinson Disease - diagnostic imaging; Parkinson Disease - drug therapy; Pyrrolidines; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tomography, Emission-Computed, Single-Photon; Tropical medicine; Parkinson's disease; Dopamine D2 receptor; 123I-IBZM SPECT; Radionuclide study; Human; Nervous system diseases; Pathogenesis; Motor system disorder; Parkinson disease; Basal ganglion; Frontal cortex; Antiparkinson agent; Density; Cerebral disorder; Chemotherapy; D2 Dopamine receptor; Central nervous system disease; Adult; Complication; Advanced stage; Degenerative disease; Levodopa; Neurological disorder; Positron emission tomography; Extrapyramidal syndrome
• ISSN: 0014-3022; 1421-9913
• DOI: 10.1159/000047962

The purpose of this study was to evaluate the contribution of the postsynaptic mechanism to the development of motor fluctuation in advanced Parkinson’s disease (PD). We used 123 I-iodobenzamide single-photon emission computed tomography to measure the striatal dopamine D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres were calculated and averaged. PD patients with fluctuating levodopa response showed a significant decrease in striatal dopamine D2 receptor densities compared to those with early (1.57 ± 0.20 vs. 1.77 ± 0.12, p = 0.009) or chronic stable PD (1.57 ± 0.20 vs. 1.77 ± 0.10, p = 0.024). We conclude that the decreased D2 receptor densities in advanced PD reduced the ‘safety factor’ for synaptic transmission and contributed to the development of motor fluctuation.