Persistent and delayed behavioral changes after nicotine treatment in adolescent rats

Despite the increasing use of tobacco by adolescents, few animal studies have addressed the neurobehavioral consequences of nicotine exposure during this period. We administered nicotine to adolescent rats via continuous infusion on postnatal days (PN) 30 through 47.5, using a dosage regimen that maintains plasma levels similar to those found in smokers or in users of the transdermal nicotine patch. Behavior in a novel open field and learning a passive avoidance task were assessed during nicotine treatment and for 2 weeks post-treatment. On PN44, during nicotine exposure, female rats showed decreased grooming, an effect not seen in males; this effect is opposite to the effects of nicotine in adult rats. Two weeks after cessation of nicotine administration, females showed deficits in locomotor activity and rearing, whereas males again were unaffected; the behavioral deficits appeared at the same age at which gender-selective brain cell damage emerges. In contrast, nicotine exposure enhanced passive avoidance, with the effect intensifying and persisting throughout the post-treatment period. These results reinforce the concept that developmental vulnerability to nicotine extends into adolescence, with patterns of drug effects different from those in earlier or later periods. The correlation of neurochemical with behavioral effects strengthens the connection between adolescent nicotine exposure and persistent functional changes that may influence drug habituation, learning and memory.