Sex and age differences in approach behavior toward a port that delivers nicotine vapor

Abstract

The goal of our laboratory is to study the mechanisms that promote nicotine use, particularly in vulnerable populations. To more closely mimic 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 of our exposure regimen. Controls received ambient air in exposure chambers. 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. Nosepoke responses in adolescent females were correlated with 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.

Keywords: e-cigarette; motivation; plumes; rat; reward.

Figure 1. Adolescent Females Display More Approach Behavior to a Port That Delivered Nicotine Vapor

Note. The data reflect mean (± SEM) nosepoke responses in a port that delivered nicotine vapor or ambient air (control) in female and male adolescent and adult rats on Day 1 and Day 14 of the exposure regimen. Individual data points are color matched to allow for comparisons in each pair of rats. The asterisks (*) denote a significant difference from controls, the daggers (†) denote a difference from males, and the at sign (@) denotes a difference from adults (p ≤ .05).

Figure 2. Adolescent Females Display a Greater Increase in Approach Behavior Over Time Relative to Day 1

Note. The data reflect mean (± SEM) nosepoke responses on Day 14 expressed as percent change from Day 1 in female and male adolescent and adult rats. Individual data points are color matched to allow for comparisons in each pair of rats. The asterisks (*) denote a significant difference from controls, the daggers (†) denote a difference from males, and the number signs (#) denote a difference from Day 1 of the exposure regimen (p ≤ .05).

Figure 3. In Adolescent Females, Approach Behavior Is Correlated with Anxiety-Like Behavior

Note. The data reflect a correlational analysis between nosepoke responses and withdrawal-induced increases in physical signs and anxiety-like behavior, which is noted as percent time spent in the closed arm of the EPM on Day 14. The asterisk (*) denotes a significant correlation between nosepoke responses and percent time spent in the closed arm of the EPM (p ≤ .05).

Figure 4. Adolescent Rats Gain More Weight Over Time than Adults

Note. The data reflect mean (± SEM) changes in body weight on Day 14 expressed as percent change from Day 1 in female and male adolescent and adult rats. Individual data points are color matched to allow for comparisons in each pair of rats. The daggers (†) denote a significant difference from males, the at sign (@) denotes a difference from adults, and the number signs (#) denote a difference from Day 1 (p ≤ .05).

Figure 5. Adolescent Females Display Higher Cotinine Levels Following Nicotine Vapor Exposure

Note. The data reflect mean (± SEM) serum cotinine levels in female and male adolescent and adult rats on Day 14 of the exposure regimen. Individual data points are color matched to allow for comparisons in each pair of rats. The asterisks (*) denote a significant difference from controls, the dagger (†) denotes a difference from males, and the at sign (@) denotes a difference from adults (p ≤ .05).