title: Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.
abstract: Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway during adolescence through drug use may produce neural alterations affecting subsequent drug consumption. Consequently, the effect of nicotine exposure on binge alcohol consumption was examined along with an assessment of the neurobiological underpinnings that drive adolescent use of these drugs. Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or nicotine (200μg/ml) for ten days. On the final four days, ethanol intake was examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed significantly more ethanol and displayed higher blood ethanol concentrations than did control mice. Autoradiographic analysis of nAChR density revealed higher epibatidine binding in frontal cortical regions in mice exposed to nicotine and ethanol compared to mice exposed to ethanol only. These data show that nicotine exposure during adolescence increases subsequent binge ethanol consumption, and may affect the number of nAChRs in regions of the brain reward pathway, specifically the frontal cortex.
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, United States; The Pennsylvania State University, Department of Biobehavioral Health, University Park, PA 16802, United States. Electronic address: xzk7@cdc.gov.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Locker
authors.affiliation: University of Colorado Boulder, Institute for Behavioral Genetics and Department of Psychology and Neuroscience, Boulder, CO 80303, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Marks
authors.affiliation: The Pennsylvania State University, Department of Biobehavioral Health, University Park, PA 16802, United States.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Kamens
authors.affiliation: The Pennsylvania State University, Department of Biobehavioral Health, University Park, PA 16802, United States.
authors.forename: Laura Cousino
authors.initials: LC
authors.lastname: Klein
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism*; D012201:Reward; D015854:Up-Regulation
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D000431:Ethanol; D009538:Nicotine; D004298:Dopamine
keywords: Adolescents; Consumption; Ethanol; Mice; Nicotine; Nicotinic acetylcholine receptors