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Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa‐induced motor complications
Author(s) -
Calon Frédéric,
Morissette Marc,
Rajput Ali H.,
Hornykiewicz Oleh,
Bédard Paul J.,
Di Paolo Thérèse
Publication year - 2003
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.10343
Subject(s) - putamen , homovanillic acid , globus pallidus , dopamine , medicine , endocrinology , parkinson's disease , dopamine receptor , levodopa , dyskinesia , dopaminergic , basal ganglia , neuroscience , receptor , chemistry , psychology , central nervous system , disease , serotonin
Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing‐off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3β‐(4‐ 125 I‐iodophenyl)tropane‐2β‐carboxylic acid isopropyl ester ([ 125 I]RTI‐121) ‐specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing‐off compared to those without. Striatal 35 S‐labeled t‐butylbicyclophosphorothionate ([ 35 S]TBPS) and [ 3 H]flunitrazepam binding to GABA A receptors were unchanged in patients with Parkinson's disease, whereas [ 125 I]CGP 64213 ‐specific binding to GABA B receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [ 3 H]Flunitrazepam binding was increased in the putamen of patients with wearing‐off compared to those without. [ 35 S]TBPS–specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABA A receptors in the putamen related to the pathophysiology of wearing‐off. The present results also suggest that an up‐regulation of GABA A receptors in the internal globus pallidus is linked to the pathogenesis of levodopa‐induced dyskinesias. © 2002 Movement Disorder Society