Nicotine has been shown to affect GABAergic function in the brain. In rats, nicotine increases GABA release acutely, and human and animal studies have implicated the GABAergic system in the acquisition and maintenance of nicotine addiction. Transient increases in levels of human cortical GABA levels have been observed by magnetic resonance spectroscopy (MRS) with nicotine administration in preliminary studies in humans. Furthermore, nicotine has been seen to elevate brain GABA synthesis 2-4 fold in human brain. Knowing the effects of acute nicotine administration on brain GABA may provide insight into the interaction of tobacco smoking with prevalent disorders that are known to involve the GABAergic system, such as depression and alcoholism. This project may also provide further information about why it is so hard for some people to stop smoking. It has been shown that menstrual cycle related changes in brain GABA levels are abolished by smoking, and that men and women have some different responses to nicotine, so this project will also explore gender-based differences in GABAergic responses in the human brain. Several questions will be answered: 1) Does acute nicotine administration increase brain GABA? 2) How long does it take brain GABA to return to pre-nicotine levels? 3) Does nicotine increase GABA synthesis? 4) Does gender affect nicotine-induced changes in brain GABA levels and rates of synthesis? The concentration and rates of synthesis of brain GABA will be measured in 40 healthy smokers (20 men, 20 women) after overnight abstinence from smoking. The measurements will be conducted twice, once with a nicotine inhaler, and once with a placebo inhaler. Exclusion criteria will include current neuropsychiatric disorders, or a recent history of such.
This work will establish what changes in GABAergic neurons in the cerebral cortex are associated with nicotine and some of the subjective feelings that people experience with nicotine. The outcomes may help to explain why some of the newer drug-based smoking cessation approaches are effective and guide the development of new approaches. The results may also contribute to our understanding of why depressed people and patients with alcohol dependence have a greater likelihood of addiction to tobacco.
|Abdallah, Chadi G; Niciu, Mark J; Fenton, Lisa R et al. (2014) Decreased occipital cortical glutamate levels in response to successful cognitive-behavioral therapy and pharmacotherapy for major depressive disorder. Psychother Psychosom 83:298-307|
|Niciu, Mark J; Mason, Graeme F (2014) Neuroimaging in Alcohol and Drug Dependence. Curr Behav Neurosci Rep 1:45-54|
|Abdallah, Chadi G; Jiang, Lihong; De Feyter, Henk M et al. (2014) Glutamate metabolism in major depressive disorder. Am J Psychiatry 171:1320-7|
|Solecki, Wojciech; Wickham, Robert J; Behrens, Shay et al. (2013) Differential role of ventral tegmental area acetylcholine and N-methyl-D-aspartate receptors in cocaine-seeking. Neuropharmacology 75:9-18|
|Herzog, Raimund I; Jiang, Lihong; Herman, Peter et al. (2013) Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest 123:1988-98|
|Jiang, Lihong; Gulanski, Barbara Irene; De Feyter, Henk M et al. (2013) Increased brain uptake and oxidation of acetate in heavy drinkers. J Clin Invest 123:1605-14|
|Gomez, Rosane; Behar, Kevin L; Watzl, June et al. (2012) Intravenous ethanol infusion decreases human cortical ?-aminobutyric acid and N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4 tesla. Biol Psychiatry 71:239-46|
|Rothman, Douglas L; De Feyter, Henk M; de Graaf, Robin A et al. (2011) 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR Biomed 24:943-57|
|Valentine, Gerald W; Mason, Graeme F; Gomez, Rosane et al. (2011) The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res 191:122-7|
|Patel, Anant B; de Graaf, Robin A; Rothman, Douglas L et al. (2010) Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR. J Cereb Blood Flow Metab 30:1200-13|
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