Susceptibility to arecoline in male C57BL/6 J mice correlates with age factor

Epidemiological investigations and clinical studies have confirmed that human chewing of betel nut is an addictive behavior, and the proportion of teenagers chewing betel nut is increasing. Previous studies have shown that adolescence shows higher sensitivity to many addictive substances compared with adulthood, and that adult susceptibility to addictive substances is usually changed after exposure to addictive substances during adolescence. However, there are no reports of age-related animal experiments on betel nut or dependence to its active ingredients. Therefore, the two-bottle choice (TBC) (experiment 1 and 2) and conditioned place preference (CPP) (experiment 3 and 4) models with mice were used in this study to explore age-related differences in intake and preference of arecoline, the alkaloid in betel nut with highest content, and to explore the effect of arecoline exposure during adolescence on the re-exposure of arecoline in adulthood in mice. The results of experiment 1 showed that the intake of 80 μg/ml arecoline in adolescent mice was significantly higher than that in adult mice. However, there was no significant difference between adult and adolescent mice in preference for arecoline at any tested concentration (5–80 μg/ml), which may be due to the significantly higher intake of total fluid in adolescent mice compared to adult mice. The preference of arecoline in adolescent mice peaked at 20 μg/ml, and in adult mice peaked at 40 μg/ml. The results of experiment 2 showed that oral arecoline (5–80 μg/ml) in mice during adolescence caused a significant increase in the intake (days 3–16) and preference (days 5–8) for 40 μg/ml arecoline in adulthood. The results of experiment 3 showed that the doses of 0.03 or 0.1 mg/kg of arecoline produced the highest CPP response in adolescent or adult mice, respectively. The results of experiment 4 showed that mice exposed to arecoline in adolescence had significantly increased the CPP scores induced by arecoline in adulthood compared to mice that were not exposed. These data suggested that adolescent mice were more sensitive to arecoline, and exposure of mice to arecoline during adolescence increased the susceptibility to arecoline in adulthood.