Alcohol and Vapourized Nicotine Co-Exposure During Adolescence Contribute Differentially to Sex-Specific Behavioural Effects in Adulthood

IntroductionCo-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. However, little is known about their long-lasting effects when combined. Here, we examined whether adolescent co-exposure to alcohol drinking and vapourized nicotine would impact reward- and cognition-related behaviours in adult male and female rats during adulthood. MethodsFour groups of male and female Sprague Dawley rats (n=8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapour daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, rats underwent behavioural testing utilizing Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference test. ResultsA sex-dependent effect was found in the two-bottle preference test in adulthood such that females had a higher intake and preference for alcohol compared to males regardless of adolescent exposure; both male and female adult rats had greater alcohol preference compared to adolescents. Male rats exposed to vapourized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behaviour. Male rats that drank alcohol with or without nicotine vapour in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapour during adolescence. ConclusionsThe present study provides evidence that co-exposure to alcohol and vapourized nicotine during adolescence in male, but not female, rats produces longterm changes in reward- and cognition-related behaviours. ImplicationsThese findings enhance our understanding of the effects of alcohol drinking and nicotine vapour exposure in adolescence. Moreover, they highlight potential sex differences that exist in the response to alcohol and nicotine vapour, underscoring the need for follow-up studies elucidating the neurobiological mechanisms that drive these sex differences, as well as the long-term effects of alcohol and nicotine vapour use.