Differential regulation of mesolimbic alpha 3/alpha 6 beta 2 and alpha 4 beta 2 nicotinic acetylcholine receptor sites and function after long-term oral nicotine to monkeys.

The Journal of Pharmacology and Experimental Therapeutics
Sarah E McCallumMaryka Quik

Abstract

Because the mesolimbic dopamine system plays a critical role in nicotine addiction/reinforcement and because nicotinic receptors regulate dopamine release, we initiated a study to evaluate the long-term effects of nicotine (>6 months at the final dose) on nicotinic acetylcholine receptor (nAChR) sites and function in the nucleus accumbens of nonhuman primates. Nicotine was given in the drinking water as this mode of administration is long-term but intermittent, thus resembling smoking in this aspect. We determined the effects of nicotine treatment on function and binding of the alpha3/alpha6beta2* and alpha4beta2* nAChRs subtypes in nucleus accumbens, a region directly implicated in the addictive effects of nicotine. To evaluate function, we measured nicotine and K+-evoked [3H]dopamine release from nucleus accumbens synaptosomes. Changes in alpha4beta2* and alpha3/alpha6beta2* nAChRs were measured using 125I-epibatidine, [125I]A85380 [5-[125I]iodo-3(2(S)-azetidinylmethoxy) pyridine] and 125I-alpha-conotoxin MII autoradiography. Chronic nicotine treatment, which led to plasma nicotine levels in the range of smokers, significantly increased nucleus accumbens alpha4beta2* nAChR sites and function compared with control. By contrast...Continue Reading

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Citations

Jun 3, 2009·Archives of General Psychiatry·Kelly P CosgroveJulie K Staley
Aug 14, 2013·Biochemical Pharmacology·Beverley M HenleyHenry A Lester
May 9, 2012·The Journal of Pharmacology and Experimental Therapeutics·Xiomara A PerezMaryka Quik
Jul 28, 2009·Annual Review of Medicine·Riju RayCaryn Lerman
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Jul 29, 2018·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Tongyuan HuMing D Li
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Apr 21, 2007·The Journal of Pharmacology and Experimental Therapeutics·David C PerryKenneth J Kellar
Aug 11, 2019·Journal of Molecular Neuroscience : MN·Jie YangGuo-Jun Chen
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Mar 1, 2019·Molecular Neuropsychiatry·Heath D SchmidtNii A Addy

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