Nicotinic receptor inactivation after acute and repeated in vivo nicotine exposures in rats

Brain Research
Robert E VannSusan E Robinson

Abstract

Nicotine tolerance is often accompanied by an upregulation of brain area nicotinic acetylcholine receptors (nAChRs) in both animal and human subjects. This upregulation has been hypothesized to result from repeated or prolonged exposures of these receptors to nicotine. To explore this further, this study examined the level of nAChR desensitization following acute and repeated nicotine administration in the male Lewis rat. Nicotine-stimulated (86)Rb(+) efflux was measured in synaptosomes prepared from the frontal cortex, hippocampus, striatum, and thalamus. Analysis of receptor functionality was achieved by calculating area-under-the-curve (AUC) for nicotine-induced fractional (86)Rb(+) efflux. Nicotine-stimulated (86)Rb(+) efflux from all brain regions was significantly less in rats that received an acute injection of 0.4 mg/kg nicotine (s.c.) 15 min prior to dissection compared to control rats. This decrease in nAChR functional status was also observed in rats treated with 1 day or 14 days of twice-daily nicotine administration. These results are consistent with the concept that acute exposure to nicotine induces rapid desensitization of nAChRs. In addition, following repeated exposure to nicotine, nAChRs did not become tolera...Continue Reading

Citations

Aug 8, 2012·Psychopharmacology·Andrew C HarrisDavid Shelley
Aug 12, 2009·Neuroscience and Biobehavioral Reviews·Peter DomeZoltan Rihmer
Jun 22, 2011·Alcoholism, Clinical and Experimental Research·Sheketha R HauserZachary A Rodd
Jul 19, 2011·Pharmacology, Biochemistry, and Behavior·Kristin M Wildeboer-Andrud, Karen E Stevens
Sep 23, 2008·Journal of Cardiovascular Pharmacology·J F ArgachaG Berkenboom
Aug 21, 2008·Anesthesia and Analgesia·Alparslan TuranChristian C Apfel

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