Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers

Inge Mick, Jim Myers, Anna C Ramos, Paul R A Stokes, David Erritzoe, Alessandro Colasanti, Roger N Gunn, Eugenii A Rabiner, Graham E Searle, Adam D Waldman, Mark C Parkin, Alan D Brailsford, José Cf Galduróz, Henrietta Bowden-Jones, Luke Clark, David J Nutt, Anne R Lingford-Hughes

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51 Citations (Scopus)
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Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. 14 PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may play an important role in the pathophysiology of addictions.Neuropsychopharmacology accepted article preview online, 10 November 2015. doi:10.1038/npp.2015.340.

Original languageEnglish
Pages (from-to)1742–1750
Issue number7
Early online date10 Nov 2015
Publication statusPublished - 1 Jun 2016


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