Blunted midbrain reward activation during smoking withdrawal: a preliminary study.

Introduction: Tobacco smoking is the leading preventable cause of death, causing more than six million deaths annually worldwide, mainly due to cardiovascular disease and cancer. Many habitual smokers try to stop smoking but only about 7% are successful, despite widespread knowledge of the risks. Development of addiction to a range of substances is associated with progressive blunting of brain reward responses and sensitisation of stress responses, as described by the allostasis theory of addiction. There is pre-clinical evidence from rodents for a dramatic decrease in brain reward function during nicotine withdrawal. Methods: Here we tested the hypothesis that habitual smokers would also exhibit blunted reward function during nicotine withdrawal using a decision-making task and fMRI. Results: Our findings supported this hypothesis, with midbrain reward-related responses particularly blunted. We also tested the hypothesis that smokers with a longer duration of smoking would have more pronounced abnormalities. Contrary to expectations, we found that a shorter duration of smoking in younger smokers was associated with the most marked abnormalities, with blunted midbrain reward related activation including the dopaminergic ventral tegmental area. Discussion: Given the substantial mortality associated with smoking, and the small percent of people who manage to achieve sustained abstinence, further translational studies on nicotine addiction mechanisms are indicated.