Naltrexone Differentially Modulates the Neural Correlates of Motor Impulse Control in Abstinent Alcohol-Dependent and Polysubstance-Dependent Individuals

Liam J. Nestor, Louise M. Paterson, Anna Murphy, John McGonigle, Csaba Orban, Laurence Reed, Eleanor Taylor, Remy Flechais, Dana Smith, Edward T. Bullmore, Karen D. Ersche, John Suckling, Rebecca Elliott, Bill Deakin, Ilan Rabiner, Anne Lingford Hughes, Barbara J. Sahakian, Trevor W. Robbins, David J. Nutt

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2311-2321
Number of pages11
JournalEuropean Journal of Neuroscience
Volume50
Issue number3
Early online date6 Nov 2018
DOIs
Publication statusPublished - 1 Aug 2019
Externally publishedYes

Fingerprint

Naltrexone
Impulsive Behavior
Alcohols
Opioid Analgesics
Placebos
Disruptive, Impulse Control, and Conduct Disorders
Alcohol Abstinence
Recurrence
Task Performance and Analysis
Alcoholics
Neurosciences
Prefrontal Cortex
Alcoholism
Magnetic Resonance Imaging
Control Groups
Pharmaceutical Preparations
Population

Cite this

Nestor, Liam J. ; Paterson, Louise M. ; Murphy, Anna ; McGonigle, John ; Orban, Csaba ; Reed, Laurence ; Taylor, Eleanor ; Flechais, Remy ; Smith, Dana ; Bullmore, Edward T. ; Ersche, Karen D. ; Suckling, John ; Elliott, Rebecca ; Deakin, Bill ; Rabiner, Ilan ; Lingford Hughes, Anne ; Sahakian, Barbara J. ; Robbins, Trevor W. ; Nutt, David J. / Naltrexone Differentially Modulates the Neural Correlates of Motor Impulse Control in Abstinent Alcohol-Dependent and Polysubstance-Dependent Individuals. In: European Journal of Neuroscience. 2019 ; Vol. 50, No. 3. pp. 2311-2321.
@article{c47e7b66c6bd4328b8cfc0ec2f193629,
title = "Naltrexone Differentially Modulates the Neural Correlates of Motor Impulse Control in Abstinent Alcohol-Dependent and Polysubstance-Dependent Individuals",
abstract = "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.",
keywords = "Addiction, Functional MRI, Impulsivity, Naltrexone",
author = "Nestor, {Liam J.} and Paterson, {Louise M.} and Anna Murphy and John McGonigle and Csaba Orban and Laurence Reed and Eleanor Taylor and Remy Flechais and Dana Smith and Bullmore, {Edward T.} and Ersche, {Karen D.} and John Suckling and Rebecca Elliott and Bill Deakin and Ilan Rabiner and {Lingford Hughes}, Anne and Sahakian, {Barbara J.} and Robbins, {Trevor W.} and Nutt, {David J.}",
year = "2019",
month = "8",
day = "1",
doi = "10.1111/ejn.14262",
language = "English",
volume = "50",
pages = "2311--2321",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

Nestor, LJ, Paterson, LM, Murphy, A, McGonigle, J, Orban, C, Reed, L, Taylor, E, Flechais, R, Smith, D, Bullmore, ET, Ersche, KD, Suckling, J, Elliott, R, Deakin, B, Rabiner, I, Lingford Hughes, A, Sahakian, BJ, Robbins, TW & Nutt, DJ 2019, 'Naltrexone Differentially Modulates the Neural Correlates of Motor Impulse Control in Abstinent Alcohol-Dependent and Polysubstance-Dependent Individuals', European Journal of Neuroscience, vol. 50, no. 3, pp. 2311-2321. https://doi.org/10.1111/ejn.14262

Naltrexone Differentially Modulates the Neural Correlates of Motor Impulse Control in Abstinent Alcohol-Dependent and Polysubstance-Dependent Individuals. / Nestor, Liam J.; Paterson, Louise M.; Murphy, Anna; McGonigle, John; Orban, Csaba; Reed, Laurence; Taylor, Eleanor; Flechais, Remy; Smith, Dana; Bullmore, Edward T.; Ersche, Karen D.; Suckling, John; Elliott, Rebecca; Deakin, Bill; Rabiner, Ilan; Lingford Hughes, Anne; Sahakian, Barbara J.; Robbins, Trevor W.; Nutt, David J.

In: European Journal of Neuroscience, Vol. 50, No. 3, 01.08.2019, p. 2311-2321.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Naltrexone Differentially Modulates the Neural Correlates of Motor Impulse Control in Abstinent Alcohol-Dependent and Polysubstance-Dependent Individuals

AU - Nestor, Liam J.

AU - Paterson, Louise M.

AU - Murphy, Anna

AU - McGonigle, John

AU - Orban, Csaba

AU - Reed, Laurence

AU - Taylor, Eleanor

AU - Flechais, Remy

AU - Smith, Dana

AU - Bullmore, Edward T.

AU - Ersche, Karen D.

AU - Suckling, John

AU - Elliott, Rebecca

AU - Deakin, Bill

AU - Rabiner, Ilan

AU - Lingford Hughes, Anne

AU - Sahakian, Barbara J.

AU - Robbins, Trevor W.

AU - Nutt, David J.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - Addiction

KW - Functional MRI

KW - Impulsivity

KW - Naltrexone

UR - http://www.scopus.com/inward/record.url?scp=85057272962&partnerID=8YFLogxK

U2 - 10.1111/ejn.14262

DO - 10.1111/ejn.14262

M3 - Article

VL - 50

SP - 2311

EP - 2321

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 3

ER -