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Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.


ABSTRACT: 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.To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges.Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging.Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England.Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18).Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions.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.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.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.

SUBMITTER: Ersche KD 

PROVIDER: S-EPMC3664786 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

Ersche Karen D KD   Bullmore Edward T ET   Craig Kevin J KJ   Shabbir Shaila S SS   Abbott Sanja S   Müller Ulrich U   Ooi Cinly C   Suckling John J   Barnes Anna A   Sahakian Barbara J BJ   Merlo-Pich Emilio V EV   Robbins Trevor W TW  

Archives of general psychiatry 20100601 6


<h4>Context</h4>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.<h4>Objective</h4>To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly a  ...[more]

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