Bibliographic entry:

Ersche KD, Bullmore ET, Craig KJ, Shabbir SS, Abbott S, Müller U, Ooi C, Suckling J, Barnes A, Sahakian BJ, Merlo-Pich EV, Robbins TW (2010) “Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.” Arch Gen Psychiatry 67(6):632-44

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.

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