title: Downregulation of striatal dopamine D2 receptors in advanced Parkinson's disease contributes to the development of motor fluctuation.
abstract: 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.
authors.affiliation: Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Hwang
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Yao
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
authors.forename: Lie-Hang
authors.initials: LH
authors.lastname: Shen
authors.forename: Gann
authors.initials: G
authors.lastname: Ting
mesh_terms: 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
chemical_list: 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