title: Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: an [11C]raclopride PET study.
abstract: 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 [(11)C]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 Sustained-Release). A cognitive task was used to stimulate dopamine release in the human study. In rats, bupropion significantly decreased [(11)C]raclopride specific binding in the striatum, consistent with increases in extracellular dopamine concentrations. In man, no significant decreases in striatal [(11)C]raclopride specific binding were observed. Levels of dopamine transporter occupancy in the rat at 11 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.
authors.affiliation: Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Alice.Egerton@iop.kcl.ac.uk
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.forename: John P
authors.initials: JP
authors.lastname: Shotbolt
authors.forename: Paul R A
authors.initials: PR
authors.lastname: Stokes
authors.forename: Ella
authors.initials: E
authors.lastname: Hirani
authors.forename: Rabia
authors.initials: R
authors.lastname: Ahmad
authors.forename: Julia M
authors.initials: JM
authors.lastname: Lappin
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Reeves
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Grasby
mesh_terms: D000328:Adult; D000818:Animals; D016642:Bupropion / Q000008:administration & dosage / Q000494:pharmacology*; D003071:Cognition / Q000502:physiology; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D020891:Raclopride; D004298:Dopamine