TY - JOUR
T1 - Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals
AU - Turton, Samuel
AU - Myers, James F.M.
AU - Mick, Inge
AU - Colasanti, Alessandro
AU - Venkataraman, Ashwin
AU - Durant, Claire
AU - Waldman, Adam
AU - Brailsford, Alan
AU - Parkin, Mark C.
AU - Dawe, Gemma
AU - Rabiner, Eugenii A.
AU - Gunn, Roger N.
AU - Lightman, Stafford L.
AU - Nutt, David J.
AU - Lingford-Hughes, Anne
PY - 2020/8/25
Y1 - 2020/8/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048956371&partnerID=8YFLogxK
U2 - 10.1038/s41380-018-0107-4
DO - 10.1038/s41380-018-0107-4
M3 - Article (Academic Journal)
C2 - 29942043
AN - SCOPUS:85048956371
SN - 1359-4184
SP - 1749-1758.
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -