For example, increased levels of such proteins (p53) and reduction of DNA were found in the hippocampus, cortex, and midbrain in adolescent rats (Trauth et al. 2000). These effects were not of the same magnitude as those seen with nicotine exposure

in utero (Levin and Slotkin 1998). Nicotine also exerts effects on numerous trophic factors (DeBry and Tiffany 2008; Son and Winzer-Serhan 2009), Inhibitors,research,lifescience,medical including upregulation of FGF (Belluardo et al. 2004), PDGF (platelet-derived growth factor), BDNF (Kenny et al. 2000), Trk A (Formaggio et al. 2010), and NGF. It is possible that exacerbated expression of these growth-supporting factors via nicotine’s agonism of nAChRs Inhibitors,research,lifescience,medical may interfere with normal neurodevelopmental processes. As nicotine’s stimulation of nAChRs is potentially more prolonged than normal cholinergic transmission, expression of NTs may be higher than U0126 order required for normal neurodevelopment, with this higher expression leading to disordered development

of neuronal architecture (Abreu-Villaca et al. Inhibitors,research,lifescience,medical 2003c). Such effects may predispose an increased risk of developing anxiety and other psychiatric disorders in later life. Therapeutic Implications for Anxiety Disorders A number of these insights may have treatment implications for anxiety-based disorders and symptoms. It is hypothesized that adaptation and desensitization of nAChRs may underpin the effect of cigarettes on anxiety and mood regulation (Mineur and Picciotto 2010), Inhibitors,research,lifescience,medical based on the association between higher smoking rates and mood dysregulation (e.g., depression) (Covey et al. 1998), animal models demonstrating antidepressant effects of acute nicotine on learned helplessness (Semba et al. 1998) and other depression behaviors (Djuric et al. 1999; Tizabi et al. 1999), the effect of antidepressants such as bupropion as smoking cessation aids (Hurt et al. 1997) and that some antidepressants

also serve as noncompetitive inhibitors of nAChRs (Shytle et al. 2002). Many of these effects apply to increased anxiety, suggesting that Inhibitors,research,lifescience,medical certain central nAChRs may serve as a new potential treatment target. Numerous studies have demonstrated potential for use of centrally acting nAChR antagonists in anxiety treatment. For example, the nAChR antagonist mecamylamine has produced anxiolytic improvement in multiple Ribonucleotide reductase animal models (Newman et al. 2002b). Mecamylamine was demonstrated to be a useful augmentation agent to SSRI treatment of major depression (George et al. 2008), and administration of mecamylamine also appears capable of blocking dexamethasone-induced anxiety, which occurs concurrently with upregulation of BDNF levels (Park et al. 2011). The anxiolytic effects of nAChR antagonism have also been confirmed using an alternative agent, lobeline (Roni and Rahman 2011). Human data on the use of nAChR antagonist for anxiety are scarce.