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Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol dependent individuals

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Title: Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol dependent individuals
Authors: Turton, S
Myers, J
Mick, I
Colasanti, A
Venkataraman, A
Durant, C
Waldman, A
Brailsford, A
Parkin, M
Rabiner, EA
Gunn, R
Lightman, S
Nutt, D
Lingford-Hughes, AR
Item Type: Journal Article
Abstract: Addiction has been proposed as a ‘reward deficient’ state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.
Issue Date: 1-Aug-2020
Date of Acceptance: 14-May-2018
URI: http://hdl.handle.net/10044/1/60048
DOI: 10.1038/s41380-018-0107-4
ISSN: 1359-4184
Publisher: Nature Publishing Group
Start Page: 1749
End Page: 1758
Journal / Book Title: Molecular Psychiatry
Volume: 25
Copyright Statement: © 2018 The Author(s). This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, aslong as you give appropriate credit to the original author(s) and thesource, provide a link to the Creative Commons license, and indicate ifchanges were made. The images or other third party material in thisarticle are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is notincluded in the article’s Creative Commons license and your intendeduse is not permitted by statutory regulation or exceeds the permitteduse, you will need to obtain permission directly from the copyrightholder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Medical Research Council (MRC)
Imperial Health Charity
Brain Tumour Research Campaign
The Brain Tumour Charity
Medical Research Council (MRC)
Funder's Grant Number: G1002226
5098
n/a
33/159
MR/N00616X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Neurosciences & Neurology
POSITRON-EMISSION-TOMOGRAPHY
EXPERIMENTAL MEDICINE PLATFORM
RECEPTOR-BINDING
BETA-ENDORPHIN
REWARD ANTICIPATION
RELAPSE PREVENTION
DOPAMINE RELEASE
VENTRAL STRIATUM
ADDICTION. PART
ICCAM PLATFORM
Psychiatry
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status: Published
Online Publication Date: 2018-06-25
Appears in Collections:Department of Medicine (up to 2019)
Faculty of Medicine
Department of Brain Sciences