Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task

Nestor, Liam J. and Murphy, Anna and McGonigle, John and Orban, Csaba and Reed, Laurence and Taylor, Eleanor and Flechais, Remy and Paterson, Louise M. and Smith, Dana and Bullmore, Edward T. and Ersche, Karen D. and Suckling, John and Tait, Roger (2017) Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task. Addiction Biology, 22 (6). pp. 1576-1589. ISSN 1355-6215

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Abstract

There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards. Naltrexone is currently licensed for alcohol and opiate dependence, and may remediate such disturbances through the blockade of MORs in fronto-striatal reward circuitry. Therefore, we examined the potential acute modulating effects of naltrexone on the anticipation of, and instrumental responding for, non-drug rewards in long-term abstinent alcoholics, alcoholic poly substance-dependent individuals and controls using a monetary incentive delay (MID) task during a randomized double blind placebo controlled functional MRI study. We report that the alcoholic poly substance-dependent group exhibited slower and less accurate instrumental responding compared to alcoholics and controls that was less evident after acute naltrexone treatment. However, naltrexone treatment was unable to remediate disturbances within fronto-striatal regions during reward anticipation and ‘missed’ rewards in either substance-dependent group. While we have not been able to identify the underlying neural mechanisms for improvement observed with naltrexone in the alcoholic poly-substance dependent group, we can confirm that both substance-dependent groups exhibit substantial neural deficits during an MID task, despite being in long-term abstinence.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Nestor, L. J., Murphy, A., McGonigle, J., Orban, C., Reed, L., Taylor, E., Flechais, R., Paterson, L. M., Smith, D., Bullmore, E. T., Ersche, K. D., Suckling, J., Tait, R., Elliott, R., Deakin, B., Rabiner, I., Lingford-Hughes, A., Nutt, D. J., Sahakian, B., Robbins, T. W., and ICCAM Consortium (2017) Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task. Addiction Biology, 22: 1576–1589 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/adb.12444/abstract This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving
Uncontrolled Keywords: Abstinence; naltrexone; reward
Subjects: G400 Computer Science
Divisions: Faculty of Computing, Engineering and the Built Environment
Faculty of Computing, Engineering and the Built Environment > School of Computing and Digital Technology
Faculty of Computing, Engineering and the Built Environment > School of Computing and Digital Technology > Cloud Computing
UoA Collections > UoA11: Computer Science and Informatics
Depositing User: $ Ian McDonald
Date Deposited: 03 Nov 2017 12:14
Last Modified: 03 Nov 2017 12:14
URI: http://www.open-access.bcu.ac.uk/id/eprint/5267

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