α6β2*-Subtype Nicotinic Acetylcholine Receptors Are More Sensitive Than α4β2*-Subtype Receptors To Regulation By Chronic Nicotine Administration
Department
neurobiology
Document Type
Article
Abstract
Nicotinic acetylcholine receptors (nAChR) of the α6β2* 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 α6β2*-nAChR are down-regulated following chronic nicotine exposure (unlike other subtypes that have been investigated - most prominently α4β2* 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 α4β2*-nAChR and α6β2*-nAChR expression. α6β2*-nAChR down-regulation by chronic nicotine exposure in dopaminergic and optic-tract nuclei was ≈three-fold more sensitive than up-regulation of α4β2*-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. © 2014 International Society for Neurochemistry.
Publication Date
1-1-2014
Publication Title
Journal of Neurochemistry
ISSN
00223042
Volume
130
Issue
2
First Page
185
Last Page
198
Digital Object Identifier (DOI)
10.1111/jnc.12721
Recommended Citation
Marks, Michael J.; Grady, Sharon R.; Salminen, Outi; Paley, Miranda A.; Wageman, Charles R.; McIntosh, J. Michael; and Whiteaker, Paul, "α6β2*-Subtype Nicotinic Acetylcholine Receptors Are More Sensitive Than α4β2*-Subtype Receptors To Regulation By Chronic Nicotine Administration" (2014). Translational Neuroscience. 387.
https://scholar.barrowneuro.org/neurobiology/387