Age-related effects of acute nicotine on behavioural and neuronal measures of anxiety.

Adolescence is considered a period of enhanced vulnerability to the initiation of tobacco use. Biological differences in the sensitivity of adolescents and adults to the anxiogenic and anxiolytic effects of nicotine may contribute to this heightened vulnerability. Here, we investigated the age-dependency of the effects of acute nicotine on anxiety-related behaviour and neurotransmission. In Experiment 1, male adolescent (P33-37) and adult (P65-69) Long-Evans rats received nicotine (0, 0.4 or 0.8 mg/kg,s.c.) prior to testing using two measures of anxiety, the elevated plus maze (EPM) and light-dark (LD) transition box. In Experiment 2, in situ hybridization was used to assess, in different male adolescent and adult rats, CRF mRNA expression in the BNST, PVN and CeA in response to acute nicotine. In the EPM, adult rats displayed less anxious behaviour than adolescents. Nicotine (0.4, 0.8 mg/kg) increased open and closed arm entries in adolescent rats, suggesting increased general activity, but it did not affect behaviour in the LD box. CRF mRNA expression was elevated in PVN of adolescent rats, relative to adults. Nicotine, however, had no effect on CRF mRNA expression in the BNST, PVN or CeA. The present findings suggest that adolescents are more sensitive to the general activational, rather than anxiety-related, effects of nicotine, and that CRF mRNA expression in stress-related brain regions does not correlate with these effects. This work further characterizes the age-related differences in the anxiety-related effects of nicotine, and provides insight into potential factors influencing vulnerability to tobacco abuse.