Nestor, Liam JLiam JNestorPaterson, Louise MLouise MPatersonMurphy, AnnaAnnaMurphyMcGonigle, JohnJohnMcGonigleOrban, CsabaCsabaOrbanReed, LaurenceLaurenceReedTaylor, EleanorEleanorTaylorFlechais, RemyRemyFlechaisSmith, DanaDanaSmithBullmore, Edward TEdward TBullmoreErsche, Karen DKaren DErscheSuckling, JohnJohnSucklingElliott, RebeccaRebeccaElliottDeakin, BillBillDeakinRabiner, IlanIlanRabinerLingford Hughes, AnneAnneLingford HughesSahakian, Barbara JBarbara JSahakianRobbins, Trevor WTrevor WRobbinsNutt, David JDavid JNutt2018-11-162019-08European Journal of Neuroscience, 2019, 50 (3), pp.2311-23210953-816Xhttp://hdl.handle.net/10044/1/64321Identifying 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 poly substance‐dependent (poly‐SUD) individuals, and controls during a randomized 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.© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.addictionfunctional MRIimpulsivitynaltrexoneICCAM ConsortiumNeurology & Neurosurgery1109 Neurosciences1702 Cognitive Sciences1701 PsychologyJournal Articlehttps://www.dx.doi.org/10.1111/ejn.14262https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14262G1000018