Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and polysubstance-dependent individuals.
Paterson, Louise M
Lingford Hughes, Anne
Nutt, David J
Eur J Neurosci
MetadataShow full item record
Nestor, L. J., Paterson, L. M., Murphy, A., McGonigle, J., Orban, C., Reed, L., Taylor, E., et al. (2019). Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and polysubstance-dependent individuals.. Eur J Neurosci, 50 (3), 2311-2321. https://doi.org/10.1111/ejn.14262
Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance-dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened 'top-down' control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no-go (GNG) task, we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent polysubstance-dependent (poly-SUD) individuals and controls during a randomised double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly-SUD groups respectively. Self-reported trait impulsivity in the poly-SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly-SUD groups, which are predicted by trait impulsivity in the poly-SUD group.
ICCAM Consortium, Humans, Substance-Related Disorders, Alcoholism, Naltrexone, Alcohol Deterrents, Magnetic Resonance Imaging, Double-Blind Method, Impulsive Behavior, Psychomotor Performance, Adult, Middle Aged, Female, Male, Young Adult, Alcohol Abstinence
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This article presents independent research funded by the MRC as part of their addiction initiative (grant number G1000018). GSK kindly funded the functional and structural MRI scans that took place at the London site for this study.
External DOI: https://doi.org/10.1111/ejn.14262
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286250
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/