Nicotine physical dependence and tolerance in the mouse following chronic oral administration

Psychopharmacology
Sheri D GrabusM I Damaj

Abstract

Although nicotine dependence and tolerance develop in rats, few studies have examined these processes in the mouse. Establishing such mouse models would eventually allow for an examination of the role of specific nicotinic receptor subtypes in mediating these processes (i.e. through the use of receptor knockouts). The goals of the present study were to establish mouse models of nicotine dependence and tolerance. Mice were chronically exposed to nicotine (0-200 mug/ml) in their drinking solution and assayed for plasma nicotine and cotinine levels, withdrawal signs following nicotine cessation (spontaneous withdrawal) or nicotinic antagonist administration (precipitated withdrawal), or nicotine tolerance. Dependence assays included somatic sign observations (paw tremors, backing and head shakes), tail-flick, plantar stimulation, elevated plus-maze and spontaneous activity. Tolerance was assayed using tail-flick, hot-plate and body temperature tests. Plasma nicotine and cotinine levels were elevated during oral nicotine exposure (15.85 ng/ml and 538.00 ng/ml, respectively) and quickly declined following nicotine cessation (<1 ng/ml and <2 ng/ml, respectively), providing evidence that the oral route was pharmacologically relevant. ...Continue Reading

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Citations

Feb 1, 2012·Human Genetics·Allison B Gold, Caryn Lerman
May 13, 2009·Acta Pharmacologica Sinica·Zheng-xiong XiEliot L Gardner
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andreas GörlichInés Ibañez-Tallon
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May 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Morgane BessonPhilippe Faure
May 17, 2012·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Sheri D GrabusMohamad Imad Damaj
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