Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications.

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 3beta-(4-(125)I-iodophenyl)tropane-2beta-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.

• Authors: Frédéric Calon, Marc Morissette, Ali H Rajput, Oleh Hornykiewicz, Paul J Bédard, Thérèse Di Paolo
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 18 Issue 3 Pg. 241-253 (Mar 2003) ISSN: 0885-3185 [Print] United States
• PMID: 12621627 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Movement Disorder Society

Chemical References

• Antiparkinson Agents
• Receptors, GABA
• Receptors, GABA-A
• Receptors, GABA-B
• Levodopa
• Dopamine

Topics

• Aged
• Aged, 80 and over
• Antiparkinson Agents (adverse effects, therapeutic use)
• Autoradiography
• Brain (metabolism)
• Case-Control Studies
• Dopamine (metabolism)
• Dyskinesia, Drug-Induced (metabolism, physiopathology)
• Female
• Globus Pallidus (metabolism)
• Humans
• Levodopa (adverse effects, therapeutic use)
• Male
• Parkinson Disease (drug therapy, metabolism)
• Postmortem Changes
• Receptors, GABA (metabolism)
• Receptors, GABA-A (metabolism)
• Receptors, GABA-B (metabolism)