PMC

Data reflect the total number of somatic signs exhibited (± SEM) in control and nicotine-treated adults experiencing spontaneous withdrawal. Separate groups of control rats received saline (n=16), U50,488 (n=17) or nor-BNI (5 mg/kg n=8; 15 mg/kg n=6). Another group of nicotine-treated rats received saline (n=10), U50,488 (n=6), or nor-BNI (5 mg/kg n=8; 15 mg/kg n= 8). Spontaneous nicotine withdrawal produced an increase in somatic signs relative to saline controls (*p ≤ 0.05). Administration of U50,488 (5 mg/kg) facilitated spontaneous withdrawal signs (†p ≤ 0.05), whereas pretreatment with nor-BNI (15 mg/kg) blocked spontaneous withdrawal signs (#p ≤ 0.05).

Data reflect % open and closed arm time (± SEM). Separate groups of adults received saline (n=16) or U50,488 in control (n=14) or nicotine-treated groups (n=16). Adolescents also received saline (n=9) or U50,488 in control (n=9) or nicotine-treated groups (n=10). In adults (Fig. 2a and b), U50,488 (5 mg/kg) decreased time spent on the open arms and increased time spent in the closed arms in both control and nicotine-treated adults relative to rats that received saline (*p ≤ 0.05). This effect was exacerbated in nicotine-treated adults relative to control adults that received U50,488 alone (†p ≤ 0.05). In adolescents (Fig. 2c and d), U50,488 (5 mg/kg) also decreased time spent on the open arms and increased time spent on the closed arms in control and nicotine-treated adolescents relative to saline controls (*p ≤ 0.05). However, this effect was not exacerbated in nicotine-treated adolescents.

Data reflect extracellular dopamine levels in the NAcc expressed as a percentage of basal values (± SEM) in control and nicotine-treated rats that were pre-treated with U50,488 as in the behavioral studies. Separate groups of adult control (n=7) and nicotine-treated (n=7) rats were included. U50,488 (5 mg/kg) significantly decreased dopamine overflow in control and nicotine-treated rats relative to baseline (*p ≤ 0.05). The decreases in dopamine were larger in nicotine-treated adults as compared to controls (†p ≤ 0.05). The figure insets reflect the mean total AUC (± SEM) following U50,488. These data show that nicotine-treated adults displayed decreases in NAcc dopamine following U50,488 that were lower relative to adult controls (†p ≤ 0.05).

Data reflect extracellular dopamine levels in the NAcc expressed as a percentage of basal values (± SEM) in control and nicotine-treated rats. Separate groups of adult control (n=9), adult nicotine-treated (n=8), adolescent control (n=7), or nicotine-treated adolescents (n=6) were included. In adults (Fig. 3a), U50,488 (5 mg/kg) significantly decreased dopamine overflow in control and nicotine-treated rats relative to baseline (*p ≤ 0.05). The decreases in dopamine were larger in nicotine-treated adults as compared to controls (†p ≤ 0.05). The figure insets reflect the mean total AUC (± SEM) following U50,488. These data show that nicotine-treated adults displayed decreases in NAcc dopamine following U50,488 that were lower relative to adult controls (†p ≤ 0.05). However, these effects were not observed in adolescent rats (Fig. 3b).

Data reflect difference scores (± SEM), which represent time spent in the initially non-preferred side after conditioning minus before conditioning. Separate groups of adults received various doses of U50,488 in control [0 (n=9), 1.5 (n=6), 2.5 (n=7), 5 (n=10), or 7.5 n=6) and nicotine-treated groups [0 (n=5), 1.5 (n=7), 2.5 (n=8), 5 (n=10), or 7.5 n=11). Adolescents also received various doses of U50,488 in control [0 (n=7), 1.5 (n=6), 2.5 (n=6), 5 (n=8), or 7.5 (n=7)] and nicotine-treated groups [0 (n=11), 1.5 (n=8), 2.5 (n=15), 5 (n=13), or 7.5 (n=9)]. In adults (Fig. 1a and b), U50,488 produced CPA in a dose-dependent manner in nicotine-treated adult rats relative to their respective saline-treated controls (*p ≤ 0.05) and relative to control rats (†p ≤ 0.05). This effect was blocked in nicotine-treated adults that were pre-treated with the KOR antagonist nor-BNI (5 mg/kg). An analysis of the mean difference score across all doses (Fig. 1b) revealed that nicotine-treated adults displayed higher overall CPA following different doses of U50,488 relative to control adults (†p ≤ 0.05). In adolescents (Fig. 1c and d); however, there were no significant differences across all groups of rats.