Effect of Chronic Adolescent Nicotine Exposure on Anxiety in Adulthood

Adolescents appear to be uniquely vulnerable to nicotine and its reinforcing effects which contributes its addictive potential (Levin et al., 2007). Additionally, chronic adolescent nicotine exposure may cause long-term changes in the brain pathways that mediate anxiety (Slawecki et al., 2003). The Bed Nucleus of the Stria Terminalis (BNST) has been suggested as part of the anxiety pathway (Walker & Davis, 2009) and has been implicated in one animal model of anxiety known as the Light Enhanced Startle Effect (LES). The research question this thesis addressed was: Will adolescent nicotine exposure cause long-lasting changes in anxiety that persist into adulthood? Based on existing literature, we hypothesized that exposing adolescent rats to nicotine would cause a change in anxiety behavior measured in LES when the animals were later tested as adults. Adolescent Sprague-Dawley rats were exposed to either nicotine (.15 mg/kg, .40 mg/kg) or saline from postnatal days 28-42. On approximately postnatal day 67 in early adulthood, the effect of earlier adolescent nicotine exposure on anxiety was assessed in the light-enhanced startle paradigm. Adult males exposed to nicotine as adolescents showed significant increases in anxiety measured in LES compared to saline controls. Conversely, adult females showed no significant changes in anxiety behavior as a result of prior adolescent nicotine exposure. These findings suggest nicotine exposure during adolescence can produce long-lasting changes in the neural pathways that mediate anxiety that persist into adulthood. Differential development of the BNST in males versus females, particularly in terms of nicotinic acetylcholine receptor density, is considered as one explanation for the observed sex differences. The possibility that nicotine may differentially affect anxiety measured in reflexive versus volitional (choice-based) response measures is also discussed in relation to how current findings may be integrated with existing literature