Initiation of smoking occurs during adolescence. Some studies found that adolescent rats develop self-administration at higher nicotine doses than adults. For the same nicotine dose, adolescents have lower plasma nicotine levels than adults, suggesting they may have faster nicotine metabolism which may contribute to the differences in nicotine-induced behaviours. This study investigated the developmental differences in rat hepatic CYP2B protein expression, in vivo and in vitro nicotine metabolism. Plasma and brain nicotine levels were lower in early-adolescents than adults, however, cotinine levels were also lower. Slower rates of cotinine formation in early-adolescents may explain their lower cotinine levels. Early-adolescents express higher total CYP2B proteins than adults, but they appear to have less of CYP2B1, the nicotine metabolizing enzyme. These findings provide a better understanding of this animal model and indicate that differences in pharmacokinetics should be considered when comparing nicotine’s effects in adolescents and adults extrapolating behavioural findings to human.

Initiation of smoking occurs during adolescence. Some studies found that adolescent rats develop self-administration at higher nicotine doses than adults. For the same nicotine dose, adolescents have lower plasma nicotine levels than adults, suggesting they may have faster nicotine metabolism which may contribute to the differences in nicotine-induced behaviours. This study investigated the developmental differences in rat hepatic CYP2B protein expression, in vivo and in vitro nicotine metabolism. Plasma and brain nicotine levels were lower in early-adolescents than adults, however, cotinine levels were also lower. Slower rates of cotinine formation in early-adolescents may explain their lower cotinine levels. Early-adolescents express higher total CYP2B proteins than adults, but they appear to have less of CYP2B1, the nicotine metabolizing enzyme. These findings provide a better understanding of this animal model and indicate that differences in pharmacokinetics should be considered when comparing nicotine’s effects in adolescents and adults extrapolating behavioural findings to human.

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