Sex-Specific Effects in Acute Nicotine Vapor Exposure on Binge Drinking and Activity in the Central Amygdala and Ventral Tegmental Area.

Introduction: The increasing prevalence of electronic nicotine delivery systems and alcohol drinking has led to increases in nicotine and alcohol co-use. However, the impact of ENDs on brain activity and binge drinking behavior is not fully understood.

Aims And Methods: We subjected female and male C57BL/6J mice to a voluntary drinking and electronic nicotine vapor exposure paradigm. We first established baseline drinking using a drinking-in-the-dark paradigm. In the third week, mice were exposed to 3 hours sessions of electronic nicotine vapor prior to ethanol access, and ethanol and water drinking levels were measured. Following the last nicotine vapor and drinking session we measured blood alcohol levels (BAL) and collected tissue to measure brain activity by cFos expression.

Results: Nicotine vapor exposure decreased both alcohol and water intake in males, only reduced ethanol intake in females, and did not alter binge alcohol intake in either sex. Nicotine and alcohol increased activity in the central amygdala in females but had no effect in males. In the ventral tegmental area (VTA) nicotine increased activity in females but alcohol did not produce any additional increases. Nicotine and alcohol-exposed males had significantly lower BAL as compared to females, suggesting sex differences in drinking patterns where males appeared to "front-load" and females drank more throughout the end of the session.

Conclusions: These results highlight important sex differences in the impact of nicotine and alcohol co-exposure and underscore the importance of further investigating the neurobiological effects of alcohol and nicotine on brain activity and metabolism in males and females.

Implications: With increasing nicotine and alcohol use, it is imperative to understand the neurobiological and behavioral consequences of co-use with a focus on sex differences. Using passive nicotine vapor inhalation and a binge drinking paradigm, we investigated the effects of nicotine and alcohol co-use in mice. We found sex differences in alcohol intake and brain activity from this poly-substance use approach. Nicotine decreased alcohol and water intake in males, only reduced alcohol intake in females, and did not change binge alcohol drinking. Alcohol and nicotine produced sex-specific increases in the central amygdala and only nicotine increased VTA activity.