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. Understanding the brain mechanisms involved in tobacco dependence is an important step toward reducing the high rate of relapse associated with current behavioral programs and phamacological treatments for smoking cessation. This proposal seeks to define the efficacy, safety and tolerability of repetitive Transcranial Magnetic Stimulation (rTMS) for treating tobacco dependence. Tobacco dependence is a serious public health problem and cigarette smokers exhibit substantial relapse following treatment. A concept central to this proposal is that """"""""quitting"""""""" necessitates a conscious choice not to smoke (to delay gratification) and this choice is influenced by the balance of activity between fronto-parietal systems that process the value of rewards and limbic systems that favor drive states leading to immediate gratification.
Aim 1 will determine how different levels of cortical excitation, induced by different rTMS frequencies, influence reward choices and how they alter cigarette consumption. Additionally, Aim 2 will determine how limbic activation due to acute nicotine withdrawal modifies these effects in aim 1. Twenty 20 non-smoking subjects and 20 active smokers will receive two levels of high frequency rTMS and comparable sham stimulation (method we developed using electrical scalp stimulation) delivered over left prefrontal cortex. Smokers will also crossover between nicotine satiation and withdrawal conditions to determine how rTMS can modify limbic activation associated with withdrawal. The Junior investigator of this project, Christine Sheffer, Ph.D., is an expert in all aspects of the development and implementation of evidence-based treatment programs for tobacco dependence and she has direct experience with the cognitive aspects of this proposal in prior work as a co-investigator on an NIH grant with Warren Bickel. Dr. Sheffer represents a new link with the UAMS College of Public Health and brings her experience in epidemiological research to the CTN. This project will instigate a translational research effort in Dr. Sheffer's work by allowing her to build on earlier training in the electrophysiological activity of the prefrontal cortex in addiction. This project is also expected to spark parallel investigations in the Molecular Core such as examining gene expression following high intensity rTMS in rodents and work in the Animal Electrophysiology Core examining the amplitude and frequency of spontaneous cortical oscillations following rTMS. The overall goal is for Dr Sheffer to gain data sufficient for winning her first R01 from the NIH.
| Odle, Angela; Allensworth-James, Melody; Childs, Gwen V (2018) The War on the Placenta: The Differing Battles of High-Fat Diet and Obesity. Endocrinology 159:1642-1643 |
| MacNicol, Melanie C; Cragle, Chad E; McDaniel, F Kennedy et al. (2017) Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2. Sci Rep 7:11503 |
| Rhee, Christopher J; Kaiser, Jeffrey R; Rios, Danielle R et al. (2016) Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. J Pediatr 174:52-6 |
| Odle, Angela Katherine; Allensworth-James, Melody; Haney, Anessa et al. (2016) Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse. Endocrinology 157:1443-56 |
| Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki et al. (2016) Stereoselective Effects of Abused ""Bath Salt"" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation. J Pharmacol Exp Ther 356:615-23 |
| Rhee, Christopher J; Kibler, Kathleen K; Easley, R Blaine et al. (2016) The Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. Acta Neurochir Suppl 122:147-50 |
| Odle, Angela K; Allensworth-James, Melody L; Akhter, Noor et al. (2016) A Sex-Dependent, Tropic Role for Leptin in the Somatotrope as a Regulator of POU1F1 and POU1F1-Dependent Hormones. Endocrinology 157:3958-3971 |
| MacNicol, Melanie C; Cragle, Chad E; Arumugam, Karthik et al. (2015) Functional Integration of mRNA Translational Control Programs. Biomolecules 5:1580-99 |
| Rhee, Christopher J; Fraser 3rd, Charles D; Kibler, Kathleen et al. (2015) Ontogeny of cerebrovascular critical closing pressure. Pediatr Res 78:71-5 |
| Odle, Angela K; Drew, Paul D; Childs, Gwen V (2015) Giant mice reveal new roles for GH in regulating the adipose immune microenvironment. Endocrinology 156:1613-5 |
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