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Stein, E. A. et al. Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Am. J. Psychiatry 155, 1009-1015

Department of Psychiatry, Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 09/1998; 155(8):1009-15. DOI: 10.1176/ajp.155.8.1009
Source: PubMed

ABSTRACT

Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates.
Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials.
Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans.
The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.

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    • "Specifically, we explored the efficacy of the proposed FC-added rtfMRI-NF method at facilitating real-time control of neuronal processes involved in resisting cigarette cravings. Brain regions implicated in cigarette cravings include ACC (Hartwell et al., 2011; Kober et al., 2010; Azizian et al., 2009; Brody et al., 2007; Smolka et al., 2006; Due, Huettel, Hall, & Rubin, 2002; Ernst et al., 2001), medial pFC (Sutherland, McHugh, Pariyadath, & Stein, 2012; Hartwell et al., 2011; Brody et al., 2007; Stein et al., 1998), OFC (Lee, Kim, & Kim, 2012; Hartwell et al., 2011; Smolka et al., 2006; Due et al., 2002), posterior cingulate cortex (Lee, Kim, & Kim, 2012; Hartwell et al., 2011; Azizian et al., 2009; Brody et al., 2007), and precuneus (Lee, Kim, & Kim, 2012; Hartwell et al., 2011; Brody et al., 2007). In addition, central reward-related regions such as the ventral striatum/nucleus accumbens, dorsal striatum, and amygdala are well known for their role in addiction, and the anterior insula is especially important in nicotine addiction (Sutherland et al., 2012; Naqvi, Rudrauf, Damasio, & Bechara, 2007). "

    Full-text · Dataset · Dec 2015
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    • "Specifically, we explored the efficacy of the proposed FC-added rtfMRI-NF method at facilitating real-time control of neuronal processes involved in resisting cigarette cravings. Brain regions implicated in cigarette cravings include ACC (Hartwell et al., 2011; Kober et al., 2010; Azizian et al., 2009; Brody et al., 2007; Smolka et al., 2006; Due, Huettel, Hall, & Rubin, 2002; Ernst et al., 2001), medial pFC (Sutherland, McHugh, Pariyadath, & Stein, 2012; Hartwell et al., 2011; Brody et al., 2007; Stein et al., 1998), OFC (Lee, Kim, & Kim, 2012; Hartwell et al., 2011; Smolka et al., 2006; Due et al., 2002), posterior cingulate cortex (Lee, Kim, & Kim, 2012; Hartwell et al., 2011; Azizian et al., 2009; Brody et al., 2007), and precuneus (Lee, Kim, & Kim, 2012; Hartwell et al., 2011; Brody et al., 2007). In addition, central reward-related regions such as the ventral striatum/nucleus accumbens, dorsal striatum, and amygdala are well known for their role in addiction, and the anterior insula is especially important in nicotine addiction (Sutherland et al., 2012; Naqvi, Rudrauf, Damasio, & Bechara, 2007). "

    Full-text · Dataset · Dec 2015
    • "Other studies have found lower GM density in the insula in smokers (compared with non-smokers) (Gallinat et al. 2006; Fritz et al. 2014), perhaps demonstrating the effect of nicotine and other constituents of tobacco smoke on this brain structure . Similarly, anticipation of nicotine administration (Gloria et al. 2009) and administration itself (Stein et al. 1998; Kobiella et al. 2014) have been found to activate the aINS across fMRI studies, indicating that nicotine intake from smoking may affect insula activity as well. "
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    ABSTRACT: Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6 months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 ± 6.7 years of age, 11 women), 14 smokers (≥10 cigarettes a day >2 years of smoking, 29.3 ± 6.0 years of age, 10 women) and 14 ex-smokers (>1 year of quitting 30.5 ± 5.7 years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dose-dependent brain network changes notably in the right anterior insula and its connection to the ACC. © 2015 Society for the Study of Addiction.
    No preview · Article · Aug 2015 · Addiction Biology
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