This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In a series of animal experiments, we have identified a potential novel site of action for nicotine. We have shown that systemic injection of nicotine led to a dose-dependent decrease in the amplitude of the sleep state-dependent, vertex recorded, P13 midlatency auditory evoked potential generated by the reticular activating system (RAS), that localized injections of a nicotinic receptor antagonist into the cholinergic arm of the RAS (the pedunculopontine nucleus [PPN]) blocked the effects of systemic nicotine on the P13 potential (a measure of level of arousal), and that localized injection of a nicotinic receptor agonist into the PPN also led to a decrease in the amplitude of the P13 potential, an effect blocked by PPN injection of a nicotinic receptor antagonist. Nicotine also decreased the hippocampal N40 potential although these effects were not affected by antagonist or agonist injections into the PPN. Nicotine administered in cigarette smoke to alert, free moving animals had similar effects on the P13 midlatency auditory evoked potential (MAEP). These results provide a potential mechanism for explaining the anxiolytic effects of nicotine and have important implications for understanding the effects of nicotine under normal and pathological conditions.
Aims 1 -3 will test the hypothesis that NIC has a direct action on PPN neurons in vivo that account for some of the effects of NIC on arousal.
Aim 1 will characterize the effects of NIC on arousal and habituation of responses to repetitive sensory input.
In Aim 2, we will determine the effects of exposure to cigarette smoke on arousal and habituation to repetitive sensory input.
Aim 3 will characterize the effects of maternal exposure to cigarette smoke during pregnancy on PPN-mediated responses in vivo.
Aims 4 and 5 are designed to test the hypothesis that PPN output is modified by female sex hormones and that these modifications affect female animals' responses to NIC.
Aim 4 will characterize the role of female sex hormones in modulating PPN-mediated responses of female rats.
Aim 5 will determine estrogen's role in modulating PPN-mediated responses of female rates to NIC. This also provides a unique opportunity to examine the effects of in utero nicotine exposure on the subsequent development of RAS-mediated activities related to arousal and attention.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-4 (02))
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University of Arkansas for Medical Sciences
Schools of Medicine
Little Rock
United States
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