1. ¹Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA
2. ²Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA
3. ³Department of Radiology, University of Michigan, Ann Arbor, MI, USA
4. ⁴Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA

Correspondence: Dr J-K Zubieta, Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109-0720, USA. Tel: +1 734 763 6843; Fax: +1 734 647 4130; E-mail: zubieta@umich.edu

Received 9 January 2006; Revised 19 June 2006; Accepted 24 June 2006; Published online 8 November 2006.

Abstract

This is a pilot examination of the hypothesis that some of the effects of smoking cigarettes in humans are mediated through nicotine activation of opioid and dopamine (DA) neurotransmission. Neuroimaging was performed using positron emission tomography and the radiotracers [¹¹C]carfentanil and [¹¹C]raclopride, labeling -opioid and DA D2 receptors, respectively. Six healthy male smokers were abstinent overnight. After radiotracer administration, subjects smoked two denicotinized cigarettes, followed 45 min later by two average nicotine cigarettes. Dynamic data were acquired over 90 min, and transformed into parametric maps of receptor availability in vivo (binding potential, BP), corresponding to low and high nicotine smoking periods and analyzed on a voxel-by-voxel basis using SPM'99 and correction for multiple comparisons. Significant activation of -opioid receptor-mediated neurotransmission from denicotinized to average nicotine conditions was observed in the right anterior cingulate cortex. DA D2 neurotransmission was activated in the ventral basal ganglia, correlating with Fagerström scale nicotine dependence scores. Lower -opioid receptor BP was also detected during the denicotinized smoking condition in the smoker group, compared to baseline scans in non-smokers, in the cingulate cortex, thalamus, ventral basal ganglia, and amygdala. These reductions were reversed during the average nicotine condition in the thalamus, ventral basal ganglia and amygdala. These data point to both the feasibility of simultaneously examining opioid and DA neurotransmission responses to smoking in humans, as well as to the need to examine non-nicotine aspects of smoking to more fully understand the behavioral effects of this drug.