Î±6Î²2*-Subtype Nicotinic Acetylcholine Receptors Are More Sensitive Than Î±4Î²2*-Subtype Receptors To Regulation By Chronic Nicotine Administration
Nicotinic acetylcholine receptors (nAChR) of the Î±6Î²2* subtype (where *indicates the possible presence of additional subunits) are prominently expressed on dopaminergic neurons. Because of this, their role in tobacco use and nicotine dependence has received much attention. Previous studies have demonstrated that Î±6Î²2*-nAChR are down-regulated following chronic nicotine exposure (unlike other subtypes that have been investigated - most prominently Î±4Î²2* nAChR). This study examines, for the first time, effects across a comprehensive chronic nicotine dose range. Chronic nicotine dose-responses and quantitative ligand-binding autoradiography were used to define nicotine sensitivity of changes in Î±4Î²2*-nAChR and Î±6Î²2*-nAChR expression. Î±6Î²2*-nAChR down-regulation by chronic nicotine exposure in dopaminergic and optic-tract nuclei was â‰ˆthree-fold more sensitive than up-regulation of Î±4Î²2*-nAChR. In contrast, nAChR-mediated [3H]-dopamine release from dopamine-terminal region synaptosomal preparations changed only in response to chronic treatment with high nicotine doses, whereas dopaminergic parameters (transporter expression and activity, dopamine receptor expression) were largely unchanged. Functional measures in olfactory tubercle preparations were made for the first time; both nAChR expression levels and nAChR-mediated functional measures changed differently between striatum and olfactory tubercles. These results show that functional changes measured using synaptosomal [3H]-DA release are primarily owing to changes in nAChR, rather than in dopaminergic, function. Â© 2014 International Society for Neurochemistry.
Journal of Neurochemistry
Digital Object Identifier (DOI)
Marks, Michael J.; Grady, Sharon R.; Salminen, Outi; Paley, Miranda A.; Wageman, Charles R.; McIntosh, J. Michael; and Whiteaker, Paul, "Î±6Î²2*-Subtype Nicotinic Acetylcholine Receptors Are More Sensitive Than Î±4Î²2*-Subtype Receptors To Regulation By Chronic Nicotine Administration" (2014). Translational Neuroscience. 387.