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
Author(s): 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 pr oposed as a ‘reward deficient’ state which is compensated for with substance use . There is growing evidence of dysregulation in the opioid system , which play s a key role in reward , underpinning addiction. L ow 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 no t help everyone with AD. We used [ 11C] c arfentanil , a s elective mu - opioid receptor (MOR) agonis t PET radioligand , to investigate endogenous opioid tone in AD for the first time . We recruited 13 abstinent male AD and 15 control p articipants who underwent two [ 11 C]carfentanil PET scans, one before and one 3 hours 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 significant ly higher MOR availability AD participants compared with HC in any region . T his 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 addiction s .
Publication Date: 25-Jun-2018
Date of Acceptance: 13-May-2018
URI: http://hdl.handle.net/10044/1/60048
ISSN: 1359-4184
Publisher: Nature Publishing Group
Journal / Book Title: Molecular Psychiatry
Copyright Statement: This paper is embargoed until publication. Once published it will be available fully open access.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: G1002226
Keywords: 11 Medical And Health Sciences
06 Biological Sciences
17 Psychology And Cognitive Sciences
Psychiatry
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Appears in Collections:Department of Medicine
Faculty of Medicine



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