title: Localization and pharmacological modulation of GABA-B receptors in the globus pallidus of parkinsonian monkeys.
abstract: Changes in GABAergic transmission in the external and internal segments of the globus pallidus (GPe and GPi) contribute to the pathophysiology of the basal ganglia network in Parkinson's disease. Because GABA-B receptors are involved in the modulation of GABAergic transmission in GPe and GPi, it is possible that changes in the functions or localization of these receptors contribute to the changes in GABAergic transmission. To further examine this question, we investigated the anatomical localization of GABA-B receptors and the electrophysiologic effects of microinjections of GABA-B receptor ligands in GPe and GPi of MPTP-treated (parkinsonian) monkeys. We found that the pattern of cellular and ultrastructural localization of the GABA-BR1 subunit of the GABA-B receptor in GPe and GPi was not significantly altered in parkinsonian monkeys. However, the magnitude of reduction in firing rate of GPe and GPi neurons produced by microinjections of the GABA-B receptor agonist baclofen was larger in MPTP-treated animals than in normal monkeys. Injections of the GABA-B receptor antagonist CGP55845A were more effective in reducing the firing rate of GPi neurons in parkinsonian monkeys than in normal animals. In addition, the injections of baclofen in GPe and GPi, or of CGP55845A in GPi lead to a significant increase in the proportion of spikes in rebound bursts in parkinsonian animals, but not in normal monkeys. Thus, despite the lack of changes in the localization of GABA-BR1 subunits in the pallidum, GABA-B receptor-mediated effects are altered in the GPe and GPi of parkinsonian monkeys. These changes in GABA-B receptor function may contribute to bursting activities in the parkinsonian state.
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Road NE, Emory University Atlanta, GA 30329, USA. agalvan@emory.edu
authors.forename: Adriana
authors.initials: A
authors.lastname: Galvan
authors.forename: Xing
authors.initials: X
authors.lastname: Hu
authors.forename: Yoland
authors.initials: Y
authors.lastname: Smith
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichmann
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004594:Electrophysiology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020267:MPTP Poisoning / Q000378:metabolism* / Q000503:physiopathology; D008253:Macaca mulatta; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D001418:Baclofen