Journal
NEUROIMAGE
Volume 50, Issue 1, Pages 260-266Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2009.11.077
Keywords
Bupropion; Dopamine; Imaging positron emission tomography; [C-11]raclopride; Striatum; Addiction; Depression; Mechanism; Smoking; Rat; Human
Funding
- Medical Research Council
- GlaxoSmithKline
- MRC [MC_U120097115] Funding Source: UKRI
- Medical Research Council [MC_U120097115] Funding Source: researchfish
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Bupropion is an effective medication in treating addiction and is widely used as an aid to smoking cessation. Bupropion inhibits striatal dopamine reuptake via dopamine transporter blockade, but it is unknown whether this leads to increased extracellular dopamine levels at clinical doses in man. The effects of bupropion on extracellular dopamine levels in the striatum were investigated using [C-11]raclopride positron emission tomography (PET) imaging in rats administered saline, 11 or 25 mg/kg bupropion i.p. and in healthy human volunteers administered either placebo or 150 mg bupropion (Zyban (R) Sustained-Release). A cognitive task was used to stimulate dopamine release in the human study. In rats, bupropion significantly decreased [C-11]raclopride specific binding in the striatum, consistent with increases in extracellular dopamine concentrations. In man, no significant decreases in striatal [C-11]raclopride specific binding were observed. Levels of dopamine transporter occupancy in the rat at I I and 25 mg/kg bupropion i.p. were higher than predicted to occur in man at the dose used. Thus, these data indicate that, at the low levels of dopamine transporter occupancy achieved in man at clinical doses, bupropion does not increase extracellular dopamine levels. These findings have important implications for understanding the mechanism of action underlying bupropions' therapeutic efficacy and for the development of novel treatments for addiction and depression. (C) 2009 Elsevier Inc. All rights reserved.
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