Medicine and Health Sciences Commons^™

Effects Of In Utero Nicotine Exposure On Immune Cell Disposition After P. Aeruginosa Lung Infection, Nayon Kang

Theses and Dissertations--Pharmacy

Current smoking cessation guidelines recommend nicotine replacement therapy (NRT) to assist pregnant smokers to quit, but this is without strong evidence for effectiveness and safety. Nicotine, the main addictive component of tobacco, is known to exert physiological effects by binding to its receptor, the nicotinic acetylcholine receptor (nAChR). Recent studies have identified the presence of nAChRs in non-neuronal cells, and in macrophages, functional alteration upon stimulation with nicotine has been documented.

To understand the impact of in utero nicotine exposure on various immune cell disposition and function, we designed preliminary studies using an in vivo model of P. aeruginosa infection. …

The Effect Of Nicotine Co-Administration On Alcohol-Induced Reactive Hippocampal Cell Proliferation During Abstinence In An Adolescent Model Of An Alcohol Use Disorder, Megan Heath

Theses and Dissertations--Pharmacy

A significant consequence of alcohol use disorders (AUDs) is hippocampal neurodegeneration. The hippocampus is responsible for learning and memory, and neurodegeneration in this brain region has been shown to result in cognitive deficits. Interestingly, some alcoholics demonstrate improvements in hippocampus-dependent functions, potentially due the phenomenon termed adult neurogenesis. Adult neurogenesis, the process by which neural stem cells (NSCs) proliferate, differentiate into neurons, migrate into the granule cell layer, and survive, occurs in two brain regions; however, this study examines only neurogenesis occurring in the subgranular zone of the hippocampal dentate gyrus. Four-day binge ethanol exposure in an animal model causes …

Design, Synthesis, And Pharmacological Evaluation Of A Series Of Novel, Guanidine And Amidine-Containing Neonicotinoid-Like Analogs Of Nicotine: Subtype-Selective Interactions At Neuronal Nicotinic-Acetylcholine Receptor., Aaron Joseph Haubner

University of Kentucky Doctoral Dissertations

The current project examined the ability of a novel series of guandine and amidine-containing nicotine analogs to interact with several native and recombinantlyexpressed mammalian neuronal nicotinic-acetylcholine receptor (nAChR) subtypes. Rational drug design methods and parallel organic synthesis was used to generate a library of guanidine-containing nicotine (NIC) analogs (AH compounds). A smaller series of amidine-containing nicotine analogs (JC compounds) were also synthesized. In total, >150 compounds were examined. Compounds were first assayed for affinity in a high-throughput [³H]epibatidine radioligand-binding screen. Lead compounds were evaluated in subtype-selective binding experiments to probe for affinity at the α₄β_{2 …}