Alcohol and Vaporized Nicotine Co-exposure During Adolescence Contribute Differentially to Sex-Specific Behavioral Effects in Adulthood

Abstract

Introduction: Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. Here, we examined whether adolescent co-exposure to alcohol drinking and vaporized nicotine would impact reward- and cognition-related behaviors in adult male and female rats during adulthood.

Aims and methods: Four groups of male and female Sprague Dawley rats (n = 8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapor for 10 minutes 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, all rats underwent behavioral testing (ie, Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference).

Results: A sex-dependent effect, not related to adolescent nicotine or alcohol exposure, on alcohol drinking in adulthood was found, such that females had a higher intake and preference for alcohol compared to males; both male and female adult rats also had greater alcohol preference compared to their alcohol preference as adolescents. Male rats exposed to vaporized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behavior. Male rats that drank alcohol with or without nicotine vapor 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 vapor during adolescence.

Conclusions: The present study provides evidence that co-exposure to alcohol and vaporized nicotine during adolescence in male, but not female, rats produces long-term changes in reward- and cognition-related behaviors.

Implications: These findings enhance our understanding of the effects of alcohol drinking and nicotine vapor exposure in adolescence. Moreover, they highlight potential sex differences that exist in the response to alcohol and nicotine vapor, 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 vapor use.

Figure 1.

Lever press and food cup entry number, probability and latency were combined into a PCA index score for each session and averaged over the 12 PCA sessions. PCA index scores are used to classify rats as sign-trackers (STs) (score +0.3 to +1.0), intermediates (Int.) (score −0.29 to +0.29) and goal-trackers (GTs) (score −1.0 to −0.3). (A) Male groups exposed to vaporized nicotine in adolescence had a higher PCA index score compared to CO males. (B) No significant differences for PCA index scores were detected in females. The data are presented as mean ± SEM. *p ≤ .05 significant difference between males that received vaporized nicotine and males that did not receive vaporized nicotine in adolescence.

Figure 2.

Effect of adolescent drug exposure on conditioned freezing behavior in male and female rats. Adolescent drug exposure significantly impaired fear acquisition in (A) males but not in (B) females. Data are presented as mean ± SEM. *p ≤ .05 significant difference between male exposure groups and CO males.