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Acute effects of cocaine on the neurobiology of cognitive control.

ABSTRACT: Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.

SUBMITTER: Garavan H

PROVIDER: S-EPMC2607334 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Acute effects of cocaine on the neurobiology of cognitive control.

Garavan Hugh H Kaufman Jacqueline N JN Hester Robert R

Philosophical transactions of the Royal Society of London. Series B, Biological sciences 20081001 1507

Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous coca ...[more]

PMID: 18640911

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Project description:The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/'liking', but having no discernible effect on dependence-related alterations in incentive salience/'wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment.

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Acute effects of cocaine on the neurobiology of cognitive control.

Publications

Acute effects of cocaine on the neurobiology of cognitive control.

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