The role of dopamine in inhibitory control in smokers and non-smokers: a
pharmacological fMRI study.
Author(s): Luijten M(1), Veltman DJ, Hester R, Smits M, Nijs IM, Pepplinkhuizen L, Franken
IH.
Affiliation(s): Author information:
(1)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.
Publication date & source: 2013, Eur Neuropsychopharmacol. , 23(10):1247-56
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.
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