Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol Dependence

Gil Leurquin-Sterk, Jenny Ceccarini*, Cleo L. Crunelle, Bart de Laat, Jef Verbeek, Stephanie Deman, Hugo Neels, Guy Bormans, Hendrik Peuskens, Koen Van Laere

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Web of Science)

Abstract

Animal studies suggest an important role for the metabotropic glutamate receptor subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human evidence is lacking. The goal of this study was to investigate cerebral mGlu5 availability in alcohol-dependent subjects versus controls using F-18-3-fluoro-5-[(pyridin-3-yl) ethynyl] benzonitrile (F-18-FPEB) PET. Methods: Dynamic 90-min F-18-FPEB scans combined with arterial blood sampling were acquired for 16 recently abstinent alcohol-dependent subjects and 32 age-matched controls. Regional mGlu5 availability was quantified by the F-18-FPEB total distribution volume using both a voxel-by-voxel and a volume-of-interest analysis with partial-volume effect correction. Alcohol consumption within the last 3 mo was assessed by questionnaires and by hair ethyl glucuronide analysis. Craving was assessed using the Desire for Alcohol Questionnaire. Results: mGlu5 availability was lower in mainly limbic regions of alcohol-dependent subjects than in controls (P < 0.05, familywise error-corrected), ranging from 14% in the posterior cingulate cortex to 36% in the caudate nucleus. Lower mGlu5 availability was associated with higher hair ethyl glucuronide levels for most regions and was related to a lower level of craving specifically in the middle frontal gyrus, cingulate cortex, and inferolateral temporal lobe. Conclusion: These findings provide human in vivo evidence that limbic mGlu5 has a role in the pathophysiology of alcohol dependence, possibly involved in a compensatory mechanism helping to reduce craving during abstinence.
Original languageEnglish
Pages (from-to)682-690
Number of pages9
JournalJournal of Nuclear Medicine
Volume59
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • PET
  • mGlu5
  • alcohol dependence
  • craving
  • MGLUR5 ANTAGONIST MPEP
  • POSITRON-EMISSION-TOMOGRAPHY
  • CONDITIONED PLACE PREFERENCE
  • HAIR ETHYL GLUCURONIDE
  • ANXIETY-LIKE SYNDROME
  • PREFERRING P RATS
  • CRAVING QUESTIONNAIRES
  • PREFRONTAL CORTEX
  • DRINKING BEHAVIOR
  • DRUG-ADDICTION

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