Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Maryka QuikSarah E McCallum

Abstract

Our recent studies show that chronic oral nicotine partially protects against striatal damage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates. To identify the cellular changes associated with this protective action, we investigated the effects of nicotine treatment on stimulus-evoked dopamine release, dopamine turnover, and synaptic plasticity in striatum from lesioned and unlesioned animals. Monkeys were chronically (6 months) treated with nicotine in the drinking water and subsequently lesioned with the dopaminergic neurotoxin MPTP (6 months) while nicotine was continued. Nigrostriatal damage increased nicotinic acetylcholine receptor (nAChR)-mediated fractional dopamine release from residual terminals, primarily through changes in alpha3*/alpha6* nAChRs. In contrast, fractional receptor-evoked dopamine release was similar to control in unlesioned and lesioned animals with chronic oral nicotine. Long-term nicotine administration also attenuated the enhanced K(+)-evoked fractional dopamine release from synaptosomes of MPTP-lesioned animals, suggesting that nicotine treatment had a generalized effect on dopaminergic function. This premise was further supported by experiments showing that nicotin...Continue Reading

Citations

Aug 18, 2009·Journal of Molecular Neuroscience : MN·Maryka QuikMichael Yeluashvili
May 9, 2012·The Journal of Pharmacology and Experimental Therapeutics·Xiomara A PerezMaryka Quik
Oct 5, 2011·Pharmacological Reviews·Maryka Quik, Susan Wonnacott
May 1, 2011·Therapeutic Advances in Chronic Disease·Jun KawamataShun Shimohama
Jun 11, 2014·Journal of Chemical Neuroanatomy·Sara FalascaGregor Rainer
Sep 1, 2007·Expert Opinion on Drug Discovery·Pm LippielloAa Mazurov
Mar 20, 2009·Lancet Neurology·Etienne C Hirsch, Stéphane Hunot
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Sep 23, 2008·Journal of Neuroscience Research·Hiroki TakeuchiShun Shimohama
Oct 26, 2007·Annals of Neurology·Maryka QuikDonato Di Monte
Jun 14, 2012·Movement Disorders : Official Journal of the Movement Disorder Society·Maryka QuikTanuja Bordia
Mar 19, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Claudia TrenkwalderBaltazar Gomez-Mancilla
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Aug 30, 2020·Annals of Clinical and Translational Neurology·Stylianos RavanidisEpaminondas Doxakis
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