Negative association of pretreatment cigarette use with smoking-induced striatal dopamine release in smokers receiving bupropion treatment

Background and Objectives: In an effort to help identify factors that maintain heavy smoking, this study tested the association of pretreatment cigarette use (cigarettes per day) with striatal dopamine release during smoking-cessation treatment. Methods: Thirteen regular smokers (≥10 cigarettes per day) were evaluated on parameters of smoking behavior, and they entered a smoking cessation treatment protocol, including bupropion administration and individual counseling for 2 months. On week 7 of treatment, 10 of the participants underwent brain scans using [¹¹C]raclopride with positron emission tomography to assess smoking-induced dopamine release in the caudate nucleus and putamen, inferred from changes in dopamine D₂-type receptor availability. Results: Receptor availability, measured as binding potential referred to non-displaceable uptake (BP_ND) in both striatal regions re-demonstrated a significant decrease after smoking a cigarette; and pre-treatment cigarette use significantly negatively correlated with smoking-induced dopamine release in the caudate. Conclusions and Significance: The negative association of cigarette use with dopamine release suggests tolerance or down-regulation of the dopamine system by chronic smoking, or a pre-existing condition that promotes more frequent smoking. This association should be regarded as preliminary evidence that warrants verification. (Am J Addict 2016;25:486–492).