Alteration of adolescent aversive nicotine response and anxiety-like behavior in nicotine-exposed rats during late lactation period

Early nicotine exposure is an important cause of further habitual tobacco smoking. Although nicotine has not only rewarding but also aversive properties, the effects of early nicotine exposure on the distinct properties of nicotine are not well known. To reveal the effects of early adolescent nicotine exposure on further persistent tobacco smoking, we demonstrated developmental changes in nicotine-related appetitive and aversive behaviors of rats exposed to nicotine during the late lactation period. Sprague-Dawley rats were injected with saline or nicotine (2, 6 and 12 mg/kg). We performed a two bottle free-choice test using escalating doses of nicotine (25, 50 and 100 μg/ml), saccharin and quinine and the open field test in both adolescent and adult rats. The rats' aversive response to nicotine was increased according to the increase in nicotine concentration. Adolescent rats showed higher nicotine preference and consumption behaviors than did adult rats at an aversive dose of nicotine. Nicotine-exposed rats increased adolescent nicotine consumption when the nicotine concentration was 12 mg/kg. We observed significant increases in anxious behaviors in adolescent nicotine-injected rats compared to saline-injected rats, but there were no alterations in adult rats. In both adolescent and adult rats, saccharin and quinine intake were not significantly different between groups. Taken together, it suggests that repeated nicotine exposure in late lactation period affect changes in aversive nicotine responses and anxious behaviors during adolescence but there is no difference in adults.