Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications
✍ Scribed by Frédéric Calon; Marc Morissette; Ali H. Rajput; Oleh Hornykiewicz; Paul J. Bédard; Thérèse Di Paolo
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 188 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0885-3185
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✦ Synopsis
Abstract
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