Modulation of synaptic GABAA receptor function by zolpidem in substantia nigra pars reticulata

Acta Pharmacologica Sinica
Li-li ZhangWing-Ho Yung

Abstract

The substantia nigra pars reticulata (SNr) constitutes one of the output centers of the basal ganglia, and its abnormal activity is believed to contribute to some basal ganglia motor disorders. Different lines of evidence revealed a major contribution of GABAA receptor-mediated synaptic inhibition in controlling the activity of SNr. The benzodiazepine binding site within the GABAA receptor is a modulation site of significant clinical interest. A high density of benzodiazepine binding sites has been reported in the rat SNr. In the present study, we investigate the effects of activating benzodiazepine binding sites in the SNr. Whole-cell patch-clamp recordings and motor behavior were applied. Superfusion of zolpidem, a benzodiazepine binding agonist, at 100 nmol/L significantly prolonged the decay time of GABAA receptor-mediated postsynaptic currents. The prolongation on decay time induced by zolpidem was sensitive to the benzodiazepine antagonist flumazenil, confirming the specificity on the benzodiazepine site. Zolpidem at 1 micromol/L exerted a stronger prolongation on the decay time. A further experiment was performed on behaving rats. A unilateral microinjection of zolpidem into the rat SNr caused a robust contralateral rota...Continue Reading

References

Oct 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R W OlsenP Lomax
Sep 15, 1994·The Journal of Physiology·M A Häusser, W H Yung
Dec 5, 1996·European Journal of Pharmacology·P Bloms-Funke, W Löscher
Apr 26, 1997·Lancet·A DanieleP Bartolomeo
May 23, 1998·Annual Review of Pharmacology and Toxicology·E Costa
Apr 21, 1999·Brain Research. Brain Research Reviews·A K Mehta, M K Ticku
Aug 6, 2000·Movement Disorders : Official Journal of the Movement Disorder Society·E RůzickaP Busek
Apr 3, 2001·Trends in Pharmacological Sciences·U RudolphH Möhler
Apr 17, 2001·The Annals of Pharmacotherapy·D K Farver, M H Khan
Jun 28, 2006·Cellular and Molecular Neurobiology·M González RamírezL Rocha

❮ Previous
Next ❯

Citations

Jul 19, 2013·Pharmaceutical Biology·Qiao-Hui DuHong Zhang
Jul 1, 2015·Frontiers in Neurology·Ritchie E Brown, James T McKenna
Jul 19, 2018·The European Journal of Neuroscience·Robert Assini, Elizabeth D Abercrombie
Jul 23, 2011·Journal of Computational Neuroscience·Jesse PalmaStephen Grossberg
Jan 27, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Xingmin WangKe-Seng Zhao
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guo-Bo XuShang-Gao Liao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.