Locomotor and stress responses to nicotine differ in adolescent and adult rats

Abstract

Since adolescence is a critical period for the initiation of tobacco use, we have systematically compared behavioral and endocrine responses to nicotine in Sprague-Dawley rats of both sexes at early adolescence (postnatal day (P) 28), mid- adolescence (P38) and adulthood (P90). Locomotion and center time in a novel open field were evaluated for 30min following intravenous injection of saline or nicotine (60microg/kg), followed by measurement of plasma corticosterone. Complex age and sex differences in behavioral and endocrine response were observed, which were dependent on the functional endpoint examined. Whereas there were age differences in nicotine effects on all functional measures, sex differences were largely restricted to adult stress-related corticosterone and center-time responses. Although significant drug effects were detected at P28 and P90, there was no effect of nicotine at P38 on any measure examined. In saline-treated males, but not females, there were significant positive correlations across age between initial ambulatory counts and both initial vertical counts and total center time. Nicotine treatment increased correlations in both sexes, and yielded a significant negative interaction between initial ambulatory counts and plasma corticosterone. The unique responses of adolescents to nicotine are consistent with an immature function of nicotinic acetylcholine receptors at this age.

Figure 1

Age differences in nicotine-induced horizontal activity. Data are collapsed across males and females for ages P28 (a), P38 (b) and adult (c) during the 30 min following i.v. injection of nicotine (30 µg/kg/injection × 2, filled symbols) or saline (open symbols), n=9–14 per group. * p<0.05, ** p<0.01(Bonferroni) significantly different from saline treatment at the same age.

Figure 2

Age differences in nicotine-induced vertical activity. Data are collapsed across males and females for ages P28 (a), P38 (b) and adult (c) during the 30 min following i.v. injection of nicotine (30 µg/kg/injection × 2, filled symbols) or saline (open symbols), n=5–8 per group. * p<0.05 (Bonferroni) significantly different from saline treatment at the same age.

Figure 3

Age differences in nicotine-induced repetitive activity. Data are collapsed across males and females for ages P28 (a), P38 (b) and adult (c) during the 30 min following i.v. injection of nicotine (30 µg/kg/injection × 2, filled symbols) or saline (open symbols), n=5–8 per group. * p<0.05 (Bonferroni) significantly different from saline treatment at the same age.

Figure 4

Age and sex differences in the anxiolytic and anxiogenic effects of nicotine. Center time (s) from male (a, c, e) and female (b, d, f) animals aged P28 (a, b), P38 (c, d) and adult (e, f) were collected during the 30 min following i.v. injection of saline (open symbols) or nicotine (30 µg/kg/injection × 2; filled symbols). n=5–8 per group. * p<0.05, ** p<0.01 (Bonferroni) significantly different from saline treatment at the same age and sex.

Figure 5

Age and sex differences in nicotine-induced corticosterone release. a) Plasma corticosterone levels in males and females, aged P28, P38 and adult, 30 min following i.v. injection of nicotine (30 µg/kg/injection × 2, male: closed bars; female: vertical bars) or saline (male: open bars; female: horizontal bars), n=5–8 per group. b) Time course of plasma corticosterone levels in P28 (squares) and adult (triangles) males, prior to or 15, 30 or 60 min after injection of nicotine (30 µg/kg/injection × 2, closed symbols) or saline (open symbols), n=5–6 per group. *p<0.01, **p<0.05, ***p<0.001 (Bonferroni) significantly different from saline treatment in the same sex. ++p<0.01(Bonferroni) significant sex differences. ##p<0.01 (Bonferroni) significant age differences. †p<0.05, †††p<0.001 (Bonferroni) significantly different from time point 0 at which no injections were conducted.