Abstract Dr. R. Buchanan
Title of Project Effects of Nicotine on Processes Mediated by the Reticular Activating System
In preliminary studies, we identified a potential novel site of action for nicotine since a) systemic injection of nicotine led to a decrease in the amplitude of the P13 potential (a measure of level of arousal generated by the reticular activating system–RAS), b) nicotinic antagonist injection into the RAS blocked the effects of systemic nicotine on arousal and habituation, and c) injection of a nicotinic agonist into the RAS also led to a decrease in the amplitude of the P13 potential. This breakthrough provides an opportunity for characterizing mechanisms that may underlie the anxiolytic and anxiogenic effects of nicotine and has important implications for the understanding of effects of nicotine under normal and pathological conditions. For example, nicotine is thought to have a calming effect on the smoker, a process that can be explained by our novel site of action for nicotine (i.e. RAS inhibition). Moreover, many schizophrenics, who suffer from hyper-arousal symptoms, smoke heavily. We suggest that this may be a form of self-medication, taking advantage of nicotine’s anxiolytic effect. We propose to characterize the effects of nicotine in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, where nicotine may exercise its anxiolytic properties. The proposed research is designed to systematically assess the effects of nicotine on pre-attentional processes (level of arousal and habituation using the P13 potential). Moreover, we will investigate these processes using systemic, intracranial injection, acute vs. chronic, and smoke exposure paradigms. These step-wise experiments will reveal sites of action and modulation of processes that will help explain some of the complex effects of this drug.
Updated 12/21/2006
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