Zolpidem modulates GABA(A) receptor function in subthalamic nucleus
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AbstractThe subthalamic nucleus occupies a position in the indirect pathway of basal ganglia circuit, which plays an important role in the movement regulation. Zolpidem is an imidazopyridine agonist with a high affinity on the benzodiazepine site of GABA(A) receptors containing alpha 1 subunit. Recently, zolpidem has been reported to be useful in treating subgroups of parkinsonian patients. A high density of zolpidem binding sites has been shown in rat subthalamic nucleus. To further investigate the modulation of zolpidem on GABAA receptor-mediated inhibitory synaptic current in subthalamic nucleus, whole-cell patch clamp recordings were used in the present study. Zolpidern at 100 nM significantly prolonged the decay time and rise time of miniature inhibitory postsynaptic currents, with no effect on the amplitude and frequency. The benzodiazepine antagonist flumazenil could completely block the potentiation induced by zolpidem, confirming the specificity on the benzodiazepine site. At a high concentration of 1 mu M, zolpidem significantly increased the decay time, rise time, amplitude and frequency of miniature inhibitory postsynaptic currents. In the behaving rats, unilateral microinjection of zolpidem into subthalamic nucleus induced a significant contralateral rotation. The present findings on the effect of zolpidem in subthalamic nucleus provide a rationale for further investigations into its potential in the treatment of Parkinson's disease. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
All Author(s) ListChen L, Xie JX, Fung KS, Yung WH
Journal nameNeuroscience Research
Volume Number58
Issue Number1
Pages77 - 85
LanguagesEnglish-United Kingdom
KeywordsGABA(A) receptor; subthalamic nucleus; zolpidem
Web of Science Subject CategoriesNeurosciences; NEUROSCIENCES; Neurosciences & Neurology

Last updated on 2020-30-06 at 05:21