Nicotine and the adolescent brain: insights from an animal model.

Tobacco use in adolescence represents one of the major challenges to the future of public health. Whereas numerous studies have explored the consequences of fetal or adult nicotine effects, little or no basic research has been conducted for nicotine during adolescence, the stage at which regular cigarette use typically begins. This review describes the recent development of a model of adolescent nicotine administration in rats that recapitulates the plasma levels of nicotine found in smokers. Adolescent nicotine evoked CNS nicotinic receptor up-regulation with a distinctly different regional pattern from that seen in the adult; increased receptor expression in male rats persisted for more than a month after discontinuing nicotine administration. We also identified evidence of cell damage and changes in cell size in the female hippocampus. These changes were accompanied by alterations in synaptic activity of cholinergic, noradrenergic, dopaminergic and serotonergic systems during nicotine administration and persisting for extended periods after the termination of exposure; behavioral alterations were commensurate with the neurochemical changes. In each case, the effects of adolescent nicotine differed not only from the adult, but also from the those seen after fetal exposure, indicating that adolescence represents a unique period of vulnerability for nicotine-induced misprogramming of brain cell development and synaptic function. Effects of nicotine on critical components of reward pathways and circuits involved in learning, memory and mood are likely to contribute to increased addictive properties and long-term behavioral problems seen in adolescent smokers.