title: Endogenous opioid release in the human brain reward system induced by acute amphetamine administration.
abstract: BACKGROUND
  We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET).
  
  
  METHODS
  Twelve healthy male volunteers underwent [(11)C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a "high" dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.25 mg total dose or approximately .017 mg/kg). Reductions in [(11)C]carfentanil binding from baseline to post-amphetamine scans (ΔBP(ND)) after the "high" and "ultra-low" amphetamine doses were assessed in 10 regions of interest.
  
  
  RESULTS
  [(11)C]carfentanil binding was reduced after the "high" but not the "ultra-low" amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior cingulate, and insula.
  
  
  CONCLUSIONS
  Our findings indicate that oral amphetamine administration induces endogenous opioid release in different areas of human brain, including basal ganglia, frontal cortex areas, and thalamus. The combination of an amphetamine challenge and [(11)C]carfentanil PET is a practical and robust method to probe the opioid system in the living human brain.
authors.affiliation: Neuropsychopharmacology Unit, Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Department of Medicine, Imperial College, London, United Kingdom. a.colasanti@imperial.ac.uk
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colasanti
authors.forename: Graham E
authors.initials: GE
authors.lastname: Searle
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Long
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Hill
authors.forename: Richard R
authors.initials: RR
authors.lastname: Reiley
authors.forename: Darren
authors.initials: D
authors.lastname: Quelch
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Andri C
authors.initials: AC
authors.lastname: Tziortzi
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Reed
authors.forename: Anne R
authors.initials: AR
authors.lastname: Lingford-Hughes
authors.forename: Adam D
authors.initials: AD
authors.lastname: Waldman
authors.forename: Koen R J
authors.initials: KR
authors.lastname: Schruers
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000378:metabolism; D005283:Fentanyl / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D012201:Reward; D018709:Statistics, Nonparametric
chemical_list: D002250:Carbon Radioisotopes; D018847:Opioid Peptides; D000661:Amphetamine; C017114:carfentanil; D005283:Fentanyl