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Functional Brain Imaging of Tobacco Exposure in Humans

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Functional Brain Imaging of Tobacco Exposure in Humans ion Res ict ea d rc d h A & f o T Storage and Brody, J Addict Res Ther 2012, S2 l h a e n r r a Journal of Addiction DOI: 10.4172/2155-6105.S2-003 u p o y J ISSN: 2155-6105 Research & Therapy Review Article Open Access Functional Brain Imaging of Tobacco Exposure in Humans Steven S Storage and Arthur L Brody* Department of Psychiatry & Biobehavioral Sciences, UCLA School of Medicine; Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, California, USA Abstract Cigarette smoking represents a major health problem in the United States. Although most cigarette smokers express a desire to quit, only about 14 to 49% will be successful after 6 or more months of treatment. An improved understanding of the acute and chronic effects of smoking on brain function may lead to more efficacious pharmacological and behavioral treatments for smoking dependence. Many research groups have utilized functional brain imaging to examine the effects of tobacco exposure on brain activity. Acute administration of nicotine and cigarette smoking itself have been found to increase activity in the prefrontal cortex, thalamus, and visual system; reduce global brain activity; and increase dopamine (DA) release in the ventral striatum/nucleus accumbens. Chronic tobacco exposure lead to an α β overall up-regulation of 4 2 nicotinic acetylcholine receptors (nAChRs) across brain regions (other than thalamus), and reduced monoamine oxidase (MAO) A and B levels in the basal ganglia. Functional brain imaging studies of cigarette craving and withdrawal, too, demonstrate important changes in brain activity. Taken together, current research suggests that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits by either direct stimulation of nAChRs, indirect stimulation through DA release of MAO inhibition, or a combination of these, and perhaps, other factors. The purpose of this review is to provide a summary of current functional brain imaging studies of tobacco use and dependence, and use this information to develop a greater understanding of brain function in smokers. Introduction uptake into the brain; brain activity responses following acute nicotine/cigarette administration; effects of pharmacologic smoking Cigarette smoking represents a major health issue in the United cessation treatment on brain activity; functional imaging of nicotinic States, and smoking cessation continues to be a difficult challenge. acetylcholine receptors; brain dopamine responses to nicotine and According to a recent survey, roughly 23% of Americans reported smoking; functional brain imaging of smoking-related cue-reactivity; smoking cigarettes [1], and while most smokers express a desire to quit functional brain imaging of cigarette withdrawal; relevance of [2], only a small minority will be successful without treatment. Even other receptors, neurotransmitter systems, and genetics to nicotine after 6 months or more of effective treatment, only approximately 14 to dependence; and future directions. 49% of smokers will achieve abstinence [3-8]. Due to the considerable health risks [9,10] and high societal costs [11,12] attributed to smoking, Nicotine Uptake into the Brain more efficacious smoking cessation treatments are urgently needed. In Numerous studies [16-18] have shown that the effects of many combination with other areas of research, functional brain imaging drugs, including nicotine, vary in relation to the rate of rise of the offers great potential for uncovering both molecular targets and brain drug’s concentration in the brain. Specifically, for drugs with addictive circuits that mediate the acute effects of smoking and the chronic potential, it is thought that faster rates of rise are associated with more effects of nicotine dependence. Knowledge of the effects of smoking on pronounced hedonic effects, thereby increasing the likelihood of brain function may lead to the creation of improved pharmacological eventual drug dependence [19,20]. Some recent studies [21,22] have and behavioral smoking cessation interventions. utilized positron emission tomography (PET) and [(11)C] nicotine to Four main imaging modalities have been utilized in functional help elucidate the cerebral kinetics of smoked nicotine. brain imaging studies of tobacco use and dependence: (1) functional In one recent study [21], PET scans of the brain were obtained in magnetic resonance imaging (fMRI), (2) positron emission 11 healthy smokers following single puffs of [(11)C] nicotine-infused tomography (PET), (3) single photon emission computed tomography cigarettes. Investigators found that a single puff was associated with a (SPECT), and (4) autoradiography. Researchers have used each of “rise time”, or the time in seconds for the [(11)C] nicotine concentration these modalities to determine the effects of acute and chronic cigarette curve to rise from 20% to 80% of its maximal value, of 11-69 seconds, smoking on brain function and smoking-related behaviors. For this and was less than 15 seconds for most patients. Noting that this rise review, the MEDLINE database was searched using keywords for each time is similar to that reported for smoked cocaine [23], the authors of the four modalities listed above cross-referenced with the words conclude that the cerebral kinetics of smoked nicotine contribute to “tobacco,” “nicotine,” and “cigarette.” Only data driven functional dependence in smokers. imaging studies were included in this review, and relevant studies from reference lists within papers found on MEDLINE were also included. In order to examine brain activity responses to acute and chronic smoking *Corresponding author: Arthur L. Brody, UCLA, Department of Psychiatry & in a cohesive fashion, this review will discuss studies of both nicotine Biobehavioral Sciences, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA and cigarettes, while acknowledging that cigarette smoke contains 90095, USA, Tel: 310-268-4778; Fax: 310-206-2802; E-mail: [email protected] thousands of constituents other than nicotine [13,14]. Additionally, Received December 12, 2011; Accepted January 23, 2012; Published January because blood flow and metabolism are closely linked under normal 25, 2012 conditions [15], functional imaging techniques that measure each of Citation: Storage SS, Brody AL (2012) Functional Brain Imaging of Tobacco these are combined under the general heading of brain activity. Exposure in Humans. J Addict Res Ther S2:003. doi:10.4172/2155-6105.S2-003 The goal of this review is to provide a comprehensive summary Copyright: © 2012 Storage SS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits of current findings from functional brain imaging studies of tobacco unrestricted use, distribution, and reproduction in any medium, provided the use and dependence. Topics covered in this review include: nicotine original author and source are credited. J Addict Res Ther Tobacco Addiction ISSN:2155-6105 JART, an open access journal Citation: Storage SS, Brody AL (2012) Functional Brain Imaging of Tobacco Exposure in Humans. J Addict Res Ther S2:003. doi:10.4172/2155-6105. S2-003 Page 2 of 10 A similarly designed study performed by Rose and colleagues smoking, the most common findings are relative increases in activity provides additional information [22]. In this study, 13 dependent in the prefrontal cortex (including the dorsolateral prefrontal cortex, smokers and 10 non-dependent smokers were imaged using PET while and inferior frontal, medial frontal, and orbitofrontal gyri) [26,35,36], smoking [(11)C]nicotine-loaded cigarettes. The authors found that, thalamus [26,36-40], and visual system [26,37-39]. Additionally, a Xe because of slower nicotine washout from the lungs, dependent smokers 133 inhalation study reported increases in frontal lobe and thalamic had a slower rate of nicotine accumulation in the brain than observed blood flow in smokers who smoked a cigarette [41]. Of these studies, in non-dependent smokers. This study, therefore, adds to the preceding those involving humans examined cigarette smokers, while those study by indicating that rate of nicotine accumulation in the brain involving animals used non-dependent rats, with strong concordance alone is not enough to explain dependency on smoked nicotine. It is of findings between each set of studies. While this group of studies clear that the link between nicotine’s kinetics in the brain and smoking demonstrate specific regional activation with cigarette smoking or behavior will be an important topic for future studies to clarify further. nicotine administration, they also imply that activation of cortico- Brain Blood Flow and Metabolic Responses Following basal ganglia-thalamic brain circuits [42] mediates the subjective effects of smoking. Zubieta et al. [43] conducted a15 O-PET study using Acute Nicotine/Cigarette Administration nicotine and denicotinized cigarettes in 19 smokers who were abstinent A fair number of functional brain imaging studies have examined of smoking for 12 hours before PET. In this study, investigators acute effects of nicotine administration or cigarette smoking compared discovered increases in the regional cerebral blood flow (rCBF) in the with a placebo or control state (Table 1). Nicotine and cigarette smoking visual cortex and cerebellum, and reductions in rCBF in the anterior have been reported to alter the activity of a wide array of brain regions; cingulate, right hippocampus, and ventral
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