An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence

A. Lingford-Hughes; J. McGonigle; I. Mick; D. Quelch; R. Flechais; D. Erritzoe; M. Bolstridge; A. Ramos; D. Meulien; D. Østergaard Nilausen; L. Breuning Sluth; C. Von Der Goltz; B. Steiniger-Brach; D. Nutt

doi:10.1093/alcalc/agv080.79

An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence

A. Lingford-Hughes, J. McGonigle, I. Mick, D. Quelch, R. Flechais, D. Erritzoe, M. Bolstridge, A. Ramos, D. Meulien, D. Østergaard Nilausen, L. Breuning Sluth, C. Von Der Goltz, B. Steiniger-Brach, D. Nutt

Research output: Contribution to journal › Conference article › peer-review

Abstract

Nalmefene is an opiate receptor modulator recently licensed for the reduction of alcohol intake in alcohol dependence. This study investigated the effects of nalmefene on anticipation of reward with alcohol dependence and high drinking risk level (>60g /day) under an alcohol clamp.

18 mg nalmefene or placebo was randomized in this cross-over, double blind study. Pulsed arterial spin labelling pre and during alcohol infusion (0.8‰) was undertaken to evaluate the impact of alcohol on blood flow. During the alcohol infusion, participants completed our fMRI protocol to assess reward, impulsivity and stress responsivity in addiction using monetary incentive delay, go-nogo and evocative tasks.

Complete data were available for 18 men. As expected, alcohol infusion resulted in an increase in blood perfusion, while treatment did not differentially impact blood perfusion. Analysis revealed a significant decrease in the contrast “reward anticipation > neutral anticipation” on nalmefene compared with placebo in the striatal ROI: t = 2.78, p = 0.013, d.f. = 17. Analysis confirmed that this was due to a decrease in BOLD response during reward, not an increase during neutral anticipation. Further, whole brain analyses observed three clusters (Z > 2.3, p < 0.05 corrected for multiple comparisons), encompassing the dorsal striatum bilaterally and parts of brain stem.

In the presence of alcohol, nalmefene pretreatment resulted in reduced BOLD response in the striatum during anticipation of reward in non-treatment seeking alcohol dependent individuals. This provides strong evidence to support the hypothesis that nalmefene's mechanism of action involves modulating the reward system.

Original language	English
Article number	P-79
Pages (from-to)	65
Number of pages	1
Journal	Alcohol and Alcoholism
Volume	50
Issue number	Issue_suppl_1
DOIs	https://doi.org/10.1093/alcalc/agv080.79
Publication status	Published - 30 Aug 2015
Externally published	Yes

Keywords

alcohol
nalmefene
placebo
adult
alcoholism
arterial spin labeling
blood flow
BOLD signal
brain analysis
brain stem
clamp
clinical article
conference abstract
controlled study
dorsal striatum
drinking
drug therapy
human
impulsiveness
infusion
male
perfusion
randomized controlled trial
reward
physiological stress

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/alcalc/agv080.79

Cite this

Lingford-Hughes, A., McGonigle, J., Mick, I., Quelch, D., Flechais, R., Erritzoe, D., Bolstridge, M., Ramos, A., Meulien, D., Østergaard Nilausen, D., Breuning Sluth, L., Von Der Goltz, C., Steiniger-Brach, B., & Nutt, D. (2015). An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence. Alcohol and Alcoholism, 50(Issue_suppl_1), 65. [P-79]. https://doi.org/10.1093/alcalc/agv080.79

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abstract = "Nalmefene is an opiate receptor modulator recently licensed for the reduction of alcohol intake in alcohol dependence. This study investigated the effects of nalmefene on anticipation of reward with alcohol dependence and high drinking risk level (>60g /day) under an alcohol clamp.18 mg nalmefene or placebo was randomized in this cross-over, double blind study. Pulsed arterial spin labelling pre and during alcohol infusion (0.8‰) was undertaken to evaluate the impact of alcohol on blood flow. During the alcohol infusion, participants completed our fMRI protocol to assess reward, impulsivity and stress responsivity in addiction using monetary incentive delay, go-nogo and evocative tasks.Complete data were available for 18 men. As expected, alcohol infusion resulted in an increase in blood perfusion, while treatment did not differentially impact blood perfusion. Analysis revealed a significant decrease in the contrast “reward anticipation > neutral anticipation” on nalmefene compared with placebo in the striatal ROI: t = 2.78, p = 0.013, d.f. = 17. Analysis confirmed that this was due to a decrease in BOLD response during reward, not an increase during neutral anticipation. Further, whole brain analyses observed three clusters (Z > 2.3, p < 0.05 corrected for multiple comparisons), encompassing the dorsal striatum bilaterally and parts of brain stem.In the presence of alcohol, nalmefene pretreatment resulted in reduced BOLD response in the striatum during anticipation of reward in non-treatment seeking alcohol dependent individuals. This provides strong evidence to support the hypothesis that nalmefene's mechanism of action involves modulating the reward system.",

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Lingford-Hughes, A, McGonigle, J, Mick, I, Quelch, D, Flechais, R, Erritzoe, D, Bolstridge, M, Ramos, A, Meulien, D, Østergaard Nilausen, D, Breuning Sluth, L, Von Der Goltz, C, Steiniger-Brach, B & Nutt, D 2015, 'An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence', Alcohol and Alcoholism, vol. 50, no. Issue_suppl_1, P-79, pp. 65. https://doi.org/10.1093/alcalc/agv080.79

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T1 - An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence

AU - Lingford-Hughes, A.

AU - McGonigle, J.

AU - Mick, I.

AU - Quelch, D.

AU - Flechais, R.

AU - Erritzoe, D.

AU - Bolstridge, M.

AU - Ramos, A.

AU - Meulien, D.

AU - Østergaard Nilausen, D.

AU - Breuning Sluth, L.

AU - Von Der Goltz, C.

AU - Steiniger-Brach, B.

AU - Nutt, D.

PY - 2015/8/30

Y1 - 2015/8/30

N2 - Nalmefene is an opiate receptor modulator recently licensed for the reduction of alcohol intake in alcohol dependence. This study investigated the effects of nalmefene on anticipation of reward with alcohol dependence and high drinking risk level (>60g /day) under an alcohol clamp.18 mg nalmefene or placebo was randomized in this cross-over, double blind study. Pulsed arterial spin labelling pre and during alcohol infusion (0.8‰) was undertaken to evaluate the impact of alcohol on blood flow. During the alcohol infusion, participants completed our fMRI protocol to assess reward, impulsivity and stress responsivity in addiction using monetary incentive delay, go-nogo and evocative tasks.Complete data were available for 18 men. As expected, alcohol infusion resulted in an increase in blood perfusion, while treatment did not differentially impact blood perfusion. Analysis revealed a significant decrease in the contrast “reward anticipation > neutral anticipation” on nalmefene compared with placebo in the striatal ROI: t = 2.78, p = 0.013, d.f. = 17. Analysis confirmed that this was due to a decrease in BOLD response during reward, not an increase during neutral anticipation. Further, whole brain analyses observed three clusters (Z > 2.3, p < 0.05 corrected for multiple comparisons), encompassing the dorsal striatum bilaterally and parts of brain stem.In the presence of alcohol, nalmefene pretreatment resulted in reduced BOLD response in the striatum during anticipation of reward in non-treatment seeking alcohol dependent individuals. This provides strong evidence to support the hypothesis that nalmefene's mechanism of action involves modulating the reward system.

AB - Nalmefene is an opiate receptor modulator recently licensed for the reduction of alcohol intake in alcohol dependence. This study investigated the effects of nalmefene on anticipation of reward with alcohol dependence and high drinking risk level (>60g /day) under an alcohol clamp.18 mg nalmefene or placebo was randomized in this cross-over, double blind study. Pulsed arterial spin labelling pre and during alcohol infusion (0.8‰) was undertaken to evaluate the impact of alcohol on blood flow. During the alcohol infusion, participants completed our fMRI protocol to assess reward, impulsivity and stress responsivity in addiction using monetary incentive delay, go-nogo and evocative tasks.Complete data were available for 18 men. As expected, alcohol infusion resulted in an increase in blood perfusion, while treatment did not differentially impact blood perfusion. Analysis revealed a significant decrease in the contrast “reward anticipation > neutral anticipation” on nalmefene compared with placebo in the striatal ROI: t = 2.78, p = 0.013, d.f. = 17. Analysis confirmed that this was due to a decrease in BOLD response during reward, not an increase during neutral anticipation. Further, whole brain analyses observed three clusters (Z > 2.3, p < 0.05 corrected for multiple comparisons), encompassing the dorsal striatum bilaterally and parts of brain stem.In the presence of alcohol, nalmefene pretreatment resulted in reduced BOLD response in the striatum during anticipation of reward in non-treatment seeking alcohol dependent individuals. This provides strong evidence to support the hypothesis that nalmefene's mechanism of action involves modulating the reward system.

KW - alcohol

KW - nalmefene

KW - placebo

KW - adult

KW - alcoholism

KW - arterial spin labeling

KW - blood flow

KW - BOLD signal

KW - brain analysis

KW - brain stem

KW - clamp

KW - clinical article

KW - conference abstract

KW - controlled study

KW - dorsal striatum

KW - drinking

KW - drug therapy

KW - human

KW - impulsiveness

KW - infusion

KW - male

KW - perfusion

KW - randomized controlled trial

KW - reward

KW - physiological stress

U2 - 10.1093/alcalc/agv080.79

DO - 10.1093/alcalc/agv080.79

M3 - Conference article

VL - 50

SP - 65

JO - Alcohol and Alcoholism

JF - Alcohol and Alcoholism

SN - 0735-0414

IS - Issue_suppl_1

M1 - P-79

ER -

An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence

Abstract

Keywords

UN SDGs

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