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. 2013 Nov 15:257:275-85.
doi: 10.1016/j.bbr.2013.10.003. Epub 2013 Oct 10.

Adolescence is a period of development characterized by short- and long-term vulnerability to the rewarding effects of nicotine and reduced sensitivity to the anorectic effects of this drug

Luis A Natividad  1 , Oscar V Torres, Theodore C Friedman, Laura E O'Dell
Affiliations

Adolescence is a period of development characterized by short- and long-term vulnerability to the rewarding effects of nicotine and reduced sensitivity to the anorectic effects of this drug

Luis A Natividad et al. Behav Brain Res. .

Abstract

This study compared nicotine intake and changes in food intake and weight gain in naïve adolescent, naïve adult, and adult rats that were exposed to nicotine during adolescence. An extended intravenous self-administration (IVSA) model was used whereby rats had 23-hour access to saline or increasing doses of nicotine (0.03, 0.06, and 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3-day periods of abstinence. Rats began IVSA as adolescents (PND 32-34) or adults (PND 75). A separate group of rats was exposed to nicotine via osmotic pumps (4.7 mg/kg) for 14 days during adolescence and then began nicotine IVSA as adults (PND 75). The rats that completed the nicotine IVSA regimen were also tested for nicotine-seeking behavior during extinction. The results revealed that nicotine intake was highest in adolescents followed by adults that were pre-exposed to nicotine during adolescence as compared to naïve adults. A similar pattern of nicotine-seeking behavior was observed during extinction. In contrast to nicotine intake, naïve adults displayed robust appetite and weight suppressant effects of nicotine, an effect that was absent in adolescents and adults that were pre-exposed to nicotine during adolescence. Our findings suggest that adolescence is a unique period of enhanced vulnerability to the reinforcing effects of nicotine. Although adolescents gain weight faster than adults, the food intake and weight suppressant effects of nicotine are reduced during adolescence. Importantly, our findings suggest that adolescent nicotine exposure produces long-lasting consequences that enhance nicotine reward and promote tolerance to the anorectic effects of this drug.

Keywords: Adolescent; Age; Food intake; Intravenous; Pre-exposure; Weight.

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Figures

Fig. 1
Fig. 1
The top graphs reflect mean operant responses (±SEM) across IVSA days in adolescent-onset (n = 6–10), naïve adult (n = 6–13), and adult rats that were pre-exposed to nicotine during adolescence (n = 9). Rats were given 23-h access to perform operant responses for saline (open symbols) or escalating doses of nicotine (filled symbols; 0.03, 0.06, or 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3-day periods of abstinence. The rats received 2 cycles of the IVSA regimen. The bottom graph reflects mean responses (±SEM) separated by the weekly dosing regimen of nicotine IVSA. Only Cycle 1 is presented in order to compare group differences in operant responses when the adolescent rats were still in the adolescent period. Asterisks (*) denote significant group differences from saline IVSA. Number signs (#) denote significant group differences from naïve adults. Double cross signs (‡) denote significant differences from the first day of IVSA at each of the 4-day intervals of testing (P ≤ 0.05).
Fig. 2
Fig. 2
The top graphs reflect operant responses for food (±SEM) across IVSA days in adolescent-onset (n = 6–10), naïve adult (n = 6–13), and adult rats that were pre-exposed to nicotine during adolescence (n = 9). Rats were given 23-h access to perform operant responses for saline (open symbols) or escalating doses of nicotine (filled symbols; 0.03, 0.06, or 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3-day periods of abstinence. The rats received 2 cycles of the IVSA regimen. The bottom graph reflects mean responses (±SEM) separated by the weekly dosing regimen of nicotine IVSA. Only Cycle 1 is presented in order to compare group differences in operant responses when the adolescent rats were still in the adolescent period. Asterisks (*) denote significant group differences from saline IVSA. Number signs (#) denote significant group differences from naïve adults (P ≤ 0.05).
Fig. 3
Fig. 3
The top graphs reflect % change in body weight (±SEM) across IVSA days in adolescent-onset (n = 6–10), naïve adult (n = 6–13), and adult rats that were pre-exposed to nicotine during adolescence (n = 9). Rats were given 23-h access to perform operant responses for saline (open symbols) or escalating doses of nicotine (filled symbols; 0.03, 0.06, or 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3-day periods of abstinence. The rats received 2 cycles of the IVSA regimen. The bottom graph reflects mean % change values (±SEM) separated by the weekly dosing regimen of nicotine IVSA. Only Cycle 1 is presented in order to compare group differences in operant responses when the adolescent rats were still in the adolescent period. Asterisks (*) denote significant group differences from saline IVSA. Number signs (#) denote significant group differences from naïve adults (P ≤ 0.05).
Fig. 4
Fig. 4
The left graph reflects operant responses (±SEM) prior to and then during extinction in adolescent-onset (n = 7), naïve adult (=10), and adult rats that were pre-exposed to nicotine during adolescence (n = 9). Extinction testing occurred first with and then without the presentation of drug cues. The right graph reflects mean responses (±SEM) separated by extinction testing in the presence and absence of drug cues. Number signs (#) denote significant group differences from naïve adults. Double cross signs (‡) denote significant differences from the average of the last 4 days of nicotine IVSA (P ≤ 0.05).
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