TY  - JOUR
T1  - INfluence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence
AU  - Ersche KD, Bullmore ET, Craig KJ, et al
Y1  - 2010/06/01
N1  - 10.1001/archgenpsychiatry.2010.60
JO  - Archives of General Psychiatry
SP  - 632
EP  - 644
VL  - 67
IS  - 6
N2  - Context 
    There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges.Objective 
    To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D2/D3 receptor antagonist and agonist challenges.Design 
    Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging.Setting 
    Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England.Participants 
    Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18).Interventions 
    Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions.Main Outcome Measures 
    Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire.Results 
    Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups.Conclusions 
    Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation by dopaminergic challenges.
SN  - 0003-990X
M3  - doi: 10.1001/archgenpsychiatry.2010.60
UR  - http://dx.doi.org/10.1001/archgenpsychiatry.2010.60
ER  -