1. ¹Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
2. ²Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
3. ³Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
4. ⁴Philadelphia VA Medical Center, University of Pennsylvania, Philadelphia, PA, USA

Correspondence: Dr TR Franklin, Department of Psychiatry, Addiction Treatment Research Center, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104, USA. Tel: +1 215 222 3200, Fax: +1 215 386 6770, E-mail: franklin_t@mail.trc.upenn.edu

Received 20 April 2006; Revised 24 January 2007; Accepted 25 January 2007; Published online 21 March 2007.

Abstract

Exposure to cigarette smoking cues can trigger physiological arousal and desire to smoke. The brain substrates of smoking cue-induced craving (CIC) are beginning to be elucidated; however, it has been difficult to study this state independent of the potential contributions of pharmacological withdrawal from nicotine. Pharmacological withdrawal itself may have substantial effects on brain activation to cues, either by obscuring or enhancing it, and as CIC is not reduced by nicotine replacement strategies, its neuro-anatomical substrates may differ. Thus, characterizing CIC is critical for developing effective interventions. This study used arterial spin-labeled (ASL) perfusion fMRI, and newly developed and highly appetitive, explicit smoking stimuli, to examine neural activity to cigarette CIC in an original experimental design that strongly minimizes contributions from pharmacological withdrawal. Twenty-one smokers (12 females) completed smoking and nonsmoking cue fMRI sessions. Craving self-reports were collected before and after each session. SPM2 software was employed to analyze data. Blood flow (perfusion) in a priori-selected regions was greater during exposure to smoking stimuli compared to nonsmoking stimuli (p<0.01; corrected) in ventral striatum, amygdala, orbitofrontal cortex, hippocampus, medial thalamus, and left insula. Perfusion positively correlated with intensity of cigarette CIC in both the dorsolateral prefrontal cortex (r²=0.54) and posterior cingulate (r²=0.53). This pattern of activation that includes the ventral striatum, a critical reward substrate, and the interconnected amygdala, cingulate and OFC, is consistent with decades of animal research on the neural correlates of conditioned drug reward.