Sex and Age Differences in Approach Behavior Toward a Port that Delivers Nicotine Vapor

The goal of our laboratory is to study the mechanisms that promote nicotine use, particularly in vulnerable populations such as adolescents and females. Thus, the purpose of this thesis was to characterize age and sex differences in the motivational/rewarding effects of nicotine (Aim 1) and withdrawal behavior (Aim 2). To more closely model human use patterns, the present study employed nicotine vapor methods involving passive exposure for 14 days in adolescent and adult female and male rats. Age and sex differences in approach behavior (nosepokes) were assessed in a port that delivered nicotine plumes on Day 1 and 14. Controls received ambient air. After the final session, rats received a nicotinic receptor antagonist to precipitate withdrawal. Then, physical signs, anxiety-like behavior, and plasma levels of cotinine (a nicotine metabolite) were assessed. Over time, females displayed a larger increase in approach behavior to the nicotine port than males, an effect that was larger in adolescents. Adolescents displayed more total physical signs of withdrawal and grooming behavior than adults, an effect that is likely related to high levels of nosepoke responses in adolescent rats. The analysis of individual signs revealed that there were no age or sex differences in the withdrawal-induced increases in teeth chatters. However, the withdrawal-induced increase in blinking behavior was higher in adult versus adolescent rats, regardless of sex. There were no group differences in anxiety-like behavior. Despite the lack of overall group differences, a correlational analysis in adolescent females revealed that nosepoke responses were positively correlated with the magnitude of anxiety-like behavior, but not physical signs of withdrawal. Adolescents gained more weight than adults regardless of treatment, and the weight gain was larger in male adolescents. Female adolescents also displayed the highest levels of cotinine than all other groups. These findings suggest that nicotine vapor produces greater motivational effects in adolescent females as compared to their adult and male counterparts