Alcohol and nicotine are common substances that are used and abused in society. Not only are these substances used independently of each other, but there is considerable overlap, with many people consuming both nicotine and alcohol. Alcohol and nicotine use are known to depend on striatal dopamine release, which is modulated by the release of acetylcholine from local cholinergic interneurons (CINs) onto dopaminergic terminals. We sought to determine whether CINs participate in self-administration of alcohol and nicotine, individually and concurrently, using a transgenic mouse with genetic deletion of the mu-opioid receptor gene Oprm1 in cholinergic (ChAT+) cells. 30 female and male mice (15 Cre- controls and 15 Cre+ experimental) were tested for consumption of 20% ethanol and a 30 μg/mL nicotine solution using a 24-hour intermittent access, two-bottle choice paradigm. The order of solution presentation was counterbalanced such that half of the mice received nicotine for two weeks, followed by ethanol for two weeks and the other half began with ethanol. In the final two weeks, all mice received a combination of ethanol and nicotine solutions. Consumption and preference for each solution (vs. water) were analyzed. Results demonstrated that Cre+ mice with CIN MOR deletion consumed similar amounts of nicotine as Cre- mice but had a lower preference for nicotine vs. water. With ethanol, there was a trend toward a sex-specific effect, with Cre+ males consuming less ethanol than Cre- wildtype males. When the combined solution was presented, Cre+ mice consumed more than Cre- mice. Finally, preference vs. water was highest for the nicotine solution among all mice. This research provides evidence that striatal CINs are involved in both ethanol and nicotine self-administration behaviors, potentially in a sex-dependent manner. Future studies will examine potential sex-dependent influences of CIN MOR deletion on ethanol consumption using a study fully powered to detect sex differences.
Authors: D.G. Lewis, C.R. Beane, N. Bruns VI, K.L. Pikus, M.H. Durfee, R.A. Zegarelli, T.W. Perry, and A.K. Radke
Advisor(s): Anna K. Radke, Department of Psychology
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