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Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals

Published version
Peer-reviewed

Type

Article

Change log

Authors

Morris, LS 
Baek, K 
Tait, R 
Elliott, R 
Ersche, KD 

Abstract

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

Description

Keywords

addiction, alcohol, cocaine, naltrexone, opiate, substance use

Journal Title

Addiction Biology

Conference Name

Journal ISSN

1355-6215
1369-1600

Volume Title

Publisher

Wiley
Sponsorship
Medical Research Council (MR/P008747/1)
The research was supported by the NIHR CRF at Imperial College Healthcare NHS Trust, the NIHR/Wellcome Trust Cambridge Research Facility and Clinical Trials Unit at Salford Royal NHS Foundation Trust. The study is supported by the North West London, Eastern and Greater Manchester NIHR Clinical Research Networks ... The following financial support was received for the research, authorship and/or publication of this article: independent research funded by the MRC as part of the addiction initiative (grant number G1000018); GSK funded the functional and structural MRI scans at Imperial College.