Adolescent nicotine exposure produces immediate and long-term changes in CNS noradrenergic and dopaminergic function

Abstract

Animal studies have only recently begun to address whether nicotine evokes unique or persistent effects on brain structure or function during adolescence, the period in which smokers typically begin their habit. In the current study, we examined the impact of adolescent nicotine treatment on catecholaminergic synaptic function in rats infused with nicotine on postnatal days 30-47.5, using a paradigm that reproduces the plasma levels of nicotine found in smokers. We assessed norepinephrine and dopamine content, turnover (an index of neural activity), and the response to an acute challenge dose of nicotine. In the midbrain, the region most closely associated with addiction, both norepinephrine and dopamine turnover were activated during the infusion period, an effect not seen in any other region for norepinephrine, and only in the striatum for dopamine. In the immediate post-infusion period (PN50-60), there was a decrement in midbrain catecholamine turnover restricted to males, whereas there was a later-emerging (PN80) activation of these pathways. Again, this pattern was not observed in any other region: the cerebral cortex showed post-treatment increases in turnover without gender selectivity, the striatum showed late-emerging deficits in dopamine turnover and the hippocampus displayed a profound deficit in noradrenergic activity that was limited to females. We also assessed the catecholaminergic response to an acute challenge with nicotine (0.3 mg/kg s.c.). The midbrain once more displayed unique properties; there was initial suppression of responses followed by post-treatment rebound elevations that were more prominent in males and eventual deficits that, in the case of dopamine, were selective for males. With the exception of the cerebellum, other regions showed the initial loss of response during the infusion period but no persistent changes in responsiveness. The current results indicate that adolescent nicotine produces immediate and long-term changes in CNS catecholaminergic systems, with regional targeting and gender selectivity corresponding to the changes seen previously in nicotinic receptor upregulation or indices of cell damage. These effects may underlie long-term behavioral changes associated with adolescent nicotine exposure.