title: The role of dopamine in inhibitory control in smokers and non-smokers: a pharmacological fMRI study.
abstract: Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of inhibitory control is still insufficiently clear. The aims of the current study were twofold. First, we investigated the role of dopamine in inhibitory control and associated brain activation. Second, the proposed link between dopamine and impaired inhibitory control in nicotine dependence was investigated by comparing smokers and non-smoking controls. Haloperidol (2 mg), a dopamine D2/D3 receptor antagonist, and placebo were administered to 25 smokers and 25 non-smoking controls in a double-blind randomized cross-over design while performing a Go/NoGo task during fMRI scanning. Haloperidol reduced NoGo accuracy and associated brain activation in the ACC, right SFG and left IFG, showing that optimal dopamine levels are crucial to effectively implement inhibitory control. In addition, smokers showed behavioral deficits on the Go/NoGo task as well as hypoactivity in the left IFG, right MFG and ACC after placebo, supporting the hypothesis of a hypoactive prefrontal system in smokers. Haloperidol had a stronger impact on prefrontal brain activation in non-smoking controls compared to smokers, which is in line with the inverted 'U' curve theory of dopamine and cognitive control. The current findings suggest that altered baseline dopamine levels in addicted individuals may contribute to the often observed reduction in inhibitory control in these populations.
authors.affiliation: Institute of Psychology, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands; Department of Radiology, Erasmus MC-University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, the Netherlands. Electronic address: luijten@fsw.eur.nl.
authors.forename: Maartje
authors.initials: M
authors.lastname: Luijten
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.forename: Robert
authors.initials: R
authors.lastname: Hester
authors.forename: Marion
authors.initials: M
authors.lastname: Smits
authors.forename: Ilse M T
authors.initials: IM
authors.lastname: Nijs
authors.forename: Lolke
authors.initials: L
authors.lastname: Pepplinkhuizen
authors.forename: Ingmar H A
authors.initials: IH
authors.lastname: Franken
mesh_terms: D000328:Adult; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004298:Dopamine