title: Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers.
abstract: 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. Fourteen 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 have an important role in the pathophysiology of addictions.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Inge
authors.initials: I
authors.lastname: Mick
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Myers
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.|Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Ramos
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.|Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Paul R A
authors.initials: PR
authors.lastname: Stokes
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.|Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Imanova Ltd., Centre for Imaging Sciences, London, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colasanti
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.|Imanova Ltd., Centre for Imaging Sciences, London, UK.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.affiliation: Imanova Ltd., Centre for Imaging Sciences, London, UK.|Department of Neuroimaging, Institute of Psychiatry, King's College, London, UK.
authors.forename: Eugenii A
authors.identifier: 0000-0003-3612-6687
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Imanova Ltd., Centre for Imaging Sciences, London, UK.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Searle
authors.affiliation: Department of Imaging, Division of Experimental Medicine, Department of Medicine, Imperial College, London, UK.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Waldman
authors.affiliation: Drug Control Centre, Analytical and Environmental Sciences, King's College London, London, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Parkin
authors.affiliation: Drug Control Centre, Analytical and Environmental Sciences, King's College London, London, UK.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Brailsford
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: José C F
authors.initials: JC
authors.lastname: Galduróz
authors.affiliation: National Problem Gambling Clinic, CNWL NHS Foundation Trust, Imperial College London, London, UK.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Bowden-Jones
authors.affiliation: Centre for Gambling Research, Department of Psychology, University of British Columbia Vancouver, Vancouver, Canada.
authors.forename: Luke
authors.initials: L
authors.lastname: Clark
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Lingford-Hughes
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage* / Q000097:blood; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000493:pharmacokinetics; D000704:Analysis of Variance; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005715:Gambling / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography
chemical_list: D000701:Analgesics, Opioid; D002247:Carbon Isotopes; D000697:Central Nervous System Stimulants; D000661:Amphetamine; C017114:carfentanil; D005283:Fentanyl