Role for α6 nicotinic receptors in l-dopa-induced dyskinesias in parkinsonian mice.

Neuropharmacology
Maryka QuikSharon R Grady

Abstract

L-Dopa-induced dyskinesias are a serious side effect that develops in most Parkinson's disease patients on dopamine replacement therapy. Few treatment options are available to manage dyskinesias; however,recent studies show that nicotine reduces these abnormal involuntary movements (AIMs) in parkinsonian animals by acting at nicotinic acetylcholine receptors (nAChRs). Identification of the nAChR subtypes that mediate this reduction in AIMs is important as it will help in the development of nAChR subtype selective drugs for their treatment. Here we investigate the role of α6β2* nAChRs, a subtype selectively present in the nigrostriatal pathway, using a6 nAChR subunit null mutant (α6⁻/⁻) mice.Wildtype and α6⁻/⁻ mice were lesioned by unilateral injection of 6-hydroxydopamine (3 mg/ml) into the medial forebrain bundle. They were then given L-dopa (3 mg/kg) plus benserazide (15 mg/kg) 2e3 wk later. L-dopa-induced AIMs developed to a similar extent in α6⁻/⁻ and wildtype mice.However, AIMs in α6⁻/⁻ mice declined to ~50% of that in wildtype mice with continued L-dopa treatment. Nicotine treatment also decreased AIMs by ~50% in wildtype mice, although not in α6⁻/⁻ mice. There were no effects on parkinsonism under any experimental condit...Continue Reading

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Citations

Feb 11, 2014·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Cheng-Long XieZhen-Guo Liu
Nov 26, 2013·Journal of Neurochemistry·Yuexiang WangRyan M Drenan
May 20, 2014·Pharmacology & Therapeutics·Maryka QuikTanuja Bordia
Jul 26, 2015·Progress in Neurobiology·Matthieu F BastideErwan Bézard
Jan 27, 2015·Frontiers in Aging Neuroscience·George E BarretoValentina Echeverria Moran
Mar 2, 2018·Journal of Neural Transmission·X A PerezM Quik
Jun 21, 2018·The European Journal of Neuroscience·Tanuja Bordia, Xiomara A Perez
Apr 12, 2019·Biomolecules·Fabio Del BelloWilma Quaglia
Aug 2, 2013·The Journal of Pharmacology and Experimental Therapeutics·Danhui ZhangMaryka Quik
Apr 27, 2020·Cellular and Molecular Neurobiology·Kamilla MussinaOlena Filchakova
Sep 28, 2018·Molecular Neurobiology·José-Rubén García-MontesRosario Moratalla
Aug 24, 2018·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Maryka QuikXiomara Perez
Dec 31, 2019·Biochemical Pharmacology·Karin Sandager-NielsenTino Dyhring

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