Investigating the sex-specific effects of socialization on voluntary ethanol self-administration in rats using an eVape system

Introduction: Peer interactions are a crucial part of social and personal development, particularly during adolescence. Adolescence is characterized as a transitional developmental period between childhood and adulthood that is often associated with increased freedom, self-exploration, and new experiences that are often peer-influenced. Due to this newfound independence, there is a higher prevalence of alcohol consumption, which is in part due to the heightened social facilitating and rewarding effects of alcohol. Previous work shows that males and females that consume excessive alcohol during adolescence are at an increased risk of developing an alcohol use disorder (AUD) later in life. However, the contributions of social interaction and sexual dimorphism in alcohol consumption, two driving factors influencing AUD risk, are not fully understood. Currently, there are several rat models used to study the characteristics of alcohol use and the emergence of AUD. However, many require the addition of a sweetener to coerce them into consuming liquid ethanol, which has been proven to confound results in adolescent rats. Here we use a novel self-administration ethanol eVape system to investigate the sexual dimorphic nature of socially facilitated ethanol consumption without the use of sweeteners. Methods: Adolescent and adult male and female Sprague-Dawley rats underwent a novel voluntary chronic intermittent self-administration ethanol vapor paradigm. Nosepoke initiated self-administration eVape chambers (La Jolla Alcohol Research, Inc.) administered 20mg/L of vaporized ethanol or air (control) into the chamber in response to each nose poke. Beginning postnatal day (PND)30 or PND70 animals were placed in vapor chambers for 4 hours every other day for a total of 40 sessions. All animals underwent 10 sessions with their cagemate (social access) followed by 10 sessions in isolation (isolated access), a 10 day forced abstinence period, 10 sessions in isolation (isolated access), and 10 sessions with their cagemate (social access). Results: These data reveal that while female rats consumed more alcohol than age-matched males, male rats increase ethanol preference regardless of age. In addition, all rats regardless of sex or age consumed more ethanol during the first social access session than during the subsequent isolated access sessions. Interestingly, there was an increase in ethanol consumption in adult females during the second social access session compared to the previous isolated access session that was not observed in males. Conclusion: These data demonstrate that female and male rats, regardless of age are vulnerable to socially facilitated ethanol consumption. This is consistent with human data that show increased levels of alcohol consumption among adolescents and young adults is associated with high levels of alcohol use within their social group. However, only male rats demonstrate escalation across sessions. This may indicate that male rats are more vulnerable to escalated drinking and the emergence of ethanol dependence compared to females regardless of peer interaction. These data demonstrate that the self-administration ethanol eVape system is an effective alternative to other methods of voluntary ethanol administration for investigating factors that contribute to alcohol use and escalation.