Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice

• Adolescent female mice were exposed to nicotine and then a binge ethanol paradigm.
• Nicotine-exposed mice had higher ethanol consumption and BEC than controls.
• nAChR density in the reward pathway was measured after nicotine and ethanol intake.
• Nicotine-exposed mice had higher epibatidine binding in cortex than controls.

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 (200 μg/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.

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