1. ¹Department of Radiology, University of Colorado at Denver Health Sciences, Denver, CO, USA
2. ²Department of Psychiatry, University of Colorado at Denver Health Sciences, Denver, CO, USA
3. ³Department of Psychology, University of Colorado at Boulder, Denver, CO, USA
4. ⁴Department of Radiology, New York University Medical Center, New York, NY, USA
5. ⁵Department of Biometrics, University of Colorado at Denver Health Sciences, Denver, CO, USA

Correspondence: Dr J Tanabe, Department of Radiology and Psychiatry, University of Colorado Health Sciences Center, Box A034, 4200 East 9th Avenue, Denver, CO 80262, USA. Tel: +1 303 372 6539; Fax: +1 303 372 6148; E-mail: jody.tanabe@uchsc.edu

Received 29 October 2006; Revised 8 March 2007; Accepted 20 March 2007; Published online 25 April 2007.

Abstract

Neural mechanisms underlying the reinforcing effects of nicotine and other drugs have been widely studied and are known to involve the ventral striatum, which is part of the mesocorticolimbic dopamine system. In contrast, mechanisms of nicotine withdrawal have received less attention although subjective withdrawal likely contributes to the difficulty of quitting. The goal of this study was to determine if nicotine withdrawal was associated with alterations of cerebral blood flow (CBF) in ventral striatum. Twelve smokers, moderately dependent on nicotine, underwent MR dynamic susceptibility contrast (DSC) imaging at baseline, after overnight withdrawal from nicotine, and after nicotine replacement. DSC images were used to calculate CBF in three regions of interest: ventral striatum, thalamus, and medial frontal cortex. Subjective withdrawal symptoms were measured at each time point. In spite of significant subjective withdrawal symptoms, there was no main effect of withdrawal on CBF in the three regions. However, there was a significant correlation between the increase in withdrawal symptoms and a reduction in thalamic CBF. In contrast to withdrawal, nicotine replacement significantly increased CBF in ventral striatum. Our findings are consistent with the known role of ventral striatum in drug reward. The lack of a main effect on withdrawal, but correlation of thalamic blood flow with withdrawal symptoms suggests that more complex mechanisms mediate the subjective features of the withdrawal state.