Beta2 Nicotine Receptor Subunits: Biomarkers for Dependence
Principal Investigator: Henry A. Lester
Funding Mechanism: National Institutes of Health- Grant
ID Number: 1R01DA036061-01A1
Award Date: 8/15/2014
Institution: California Institute of Technology
Nicotine dependence is the tobacco-related disorder that underlies tobacco-related diseases. Ongoing exposure to nicotine produces upregulation of beta2 nicotinic acetylcholine receptors (nAChRs), which is associated with nicotine dependence. Menthol may increase nicotine dependence by affecting neurons, increasing nicotine absorption through airway epithelium, and/or decreasing the breakdown of nicotine. The goal of this project is to develop a production-level assay for determining the upregulation of beta2 nAChRs in a mouse model. Specific aims are: (1) to develop an efficient, quantitative, low-resolution approach based on the immunoblot technique (“western blots”) for quantifying the amount of beta2 subunits in various regions of mouse brain; (2) to develop a higher resolution, semi-quantitative approach based on fluorescence that identifies the neuronal cell types and the subcellular regions where upregulation occurs; and (3) to use these tools to test the hypothesis that menthol upregulates nAChRs even when delivered intravenously. Establishing a biomarker for nicotine dependence in mice, and then using this biomarker to investigate menthol’s actions, may contribute to tobacco-related research activities.