Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.
BACKGROUND
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 D(2)/D(3) receptor antagonist and agonist challenges.


METHODS
Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging.


METHODS
Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England.


METHODS
Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18).


METHODS
Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions.


METHODS
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.
Ersche
Karen D
KD
University of Cambridge, Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, Cambridge, England. ke220@cam.ac.uk
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
D000328:Adult; D000077582:Amisulpride; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D052160:Benzothiazoles; D015982:Bias; D002525:Cerebellar Cortex / Q000187:drug effects / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003192:Compulsive Behavior / Q000503:physiopathology / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004739:England; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D000077487:Pramipexole; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D057190:Stroop Test / Q000706:statistics & numerical data*; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011795:Surveys and Questionnaires
D052160:Benzothiazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013469:Sulpiride; D000077582:Amisulpride; D000077487:Pramipexole; D004298:Dopamine