Morris, Laurel S., Baek, Kwangyeol, Tait, Roger, Elliott, Rebecca, Ersche, Karen D., Flechais, Remy, McGonigle, John, Murphy, Anna, Nestor, Liam J., Orban, Csaba, Passetti, Filippo, Paterson, Louise M., Rabiner, Ilan, Reed, Laurence, Smith, Dana, Suckling, John, Taylor, Eleanor M., Bullmore, Edward T., Lingford-Hughes, Anne R., Deakin, Bill, Nutt, David J., Sahakian, Barbara J., Robbins, Trevor W. and Voon, Valerie (2017) Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals. Addiction Biology. ISSN 1369-1600

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiateaddiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In thecurrent study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes asso-ciated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthyvolunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance im-aging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed networkcompared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patientgroups, indicating clustered and segregated network topology and information processing. Naltrexone normalizedheightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy vol-unteers. 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 asa potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggestone possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

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