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The Journal of Neuroscience, December 19, 2007, 27(51):14035-14040; doi:10.1523/JNEUROSCI.2966-07.2007

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Behavioral/Systems/Cognitive
Neural Substrates of Abstinence-Induced Cigarette Cravings in Chronic Smokers

Ze Wang,¹ Myles Faith,² Freda Patterson,³ Kathy Tang,³ Kia Kerrin,³ E. Paul Wileyto,³ John A. Detre,¹ and Caryn Lerman³

¹Department of Neurology, Center for Functional Neuroimaging, ²Weight and Eating Disorders Program, and ³Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Correspondence should be addressed to either of the following: Dr. Ze Wang, Department of Neurology, Center for Functional Neuroimaging, University of Pennsylvania, 3400 Spruce Street, 3W Gates Building, Philadelphia, PA 19104, Email: zewang{at}mail.med.upenn.edu; or Dr. Caryn Lerman, Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104, Email: clerman{at}mail.med.upenn.edu

Craving is a hallmark of drug dependence, including dependence on nicotine. Many studies have examined the neural substrates of cravings elicited by smoking-related cues. Less is known about the neural basis of unprovoked, abstinence-induced cravings, despite the contributions of such cravings to smoking relapse. To fill this gap, we used arterial spin labeled (ASL) perfusion magnetic resonance imaging to characterize the neural substrates of abstinence-induced cravings to smoke. Fifteen chronic smokers were scanned during a resting state on two separate occasions: (1) smoking satiety and (2) abstinence (after 12 h of smoking deprivation), in counterbalanced order. Smoking abstinence state (vs satiety) was associated with increased cerebral blood flow (CBF) in anterior cingulate cortex (ACC)/medial orbitofrontal cortex (OFC) and left OFC. Abstinence-induced cravings to smoke were predicted by CBF increases (abstinence minus satiety) in the right OFC, right dorsolateral prefrontal cortex, occipital cortex, ACC, ventral striatum/nucleus accumbens, thalamus, amygdala, bilateral hippocampus, left caudate, and right insula. These data suggest that increased activation in the brain's visuospatial and reward circuitry underlies abstinence-induced cravings to smoke, and thereby, may be important in relapse.

Key words: addiction; cerebral blood flow; cortex; mesolimbic; nicotine; neuroimaging

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Received June 29, 2007; revised Oct. 12, 2007; accepted Nov. 3, 2007.

Correspondence should be addressed to either of the following: Dr. Ze Wang, Department of Neurology, Center for Functional Neuroimaging, University of Pennsylvania, 3400 Spruce Street, 3W Gates Building, Philadelphia, PA 19104, Email: zewang{at}mail.med.upenn.edu; or Dr. Caryn Lerman, Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104, Email: clerman{at}mail.med.upenn.edu

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