Downregulation of striatal dopamine D2 receptors in advanced Parkinson's disease contributes to the development of motor fluctuation.
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 123I-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.
Hwang
Wen-Jun
WJ
Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yao
Wei-Jen
WJ
Wey
Shiaw-Pyng
SP
Shen
Lie-Hang
LH
Ting
Gann
G
D000328:Adult; D000368:Aged; D001549:Benzamides; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects*; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D007980:Levodopa; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide