Sex differences in voluntary oral nicotine consumption by adolescent mice: a dose-response experiment.

Recent studies with adolescent rodents offer valuable information regarding the neurochemical and behavioral effects of adolescent nicotine exposure. One hundred twenty-one male and 125 female adolescent (35 days of age) C57BL/6J mice were tested for voluntary nicotine consumption by providing 24-h access to both saccharin-only (SAC) and one of six nicotine-containing solutions [10, 25, 50, 75, 100, 200 ug (-)-freebase nicotine/ml in 2% SAC] in the home cage for 7 days. Although males and females drank similar volumes (ml) of nicotine, the female mice consumed more nicotine adjusted for body weight (mg/kg) and as a percentage of total fluid intake than did the male mice. In contrast, there was no sex difference in overall serum cotinine levels (adjusted for liver weight). For all mice, nicotine consumption and serum cotinine levels increased in a dose-dependent manner, and the volume of nicotine intake (ml), percent nicotine intake, and nicotine dosage (mg/kg) on the last day of the experiment were positively correlated with cotinine levels. Cotinine levels were inversely related to body weight only for females. Sex differences in nicotine consumption, but not in cotinine levels, suggest sex differences in pharmacokinetic processes that may contribute to oral nicotine consumption behavior during periadolescence.