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Lower limbic metabotropic glutamate receptor 5 availability in alcohol dependence

Journal Contribution - Journal Article

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 patients versus controls using 18F-FPEB positron emission tomography. Methods: Dynamic 90 minute 18F-FPEB scans combined with arterial blood sampling were acquired in 16 recently abstinent alcohol-dependent patients and 32 age-matched controls. Regional mGlu5 availability was quantified by the 18F-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 months 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 patients compared to controls (P<0.05, family-wise error corrected), ranging from 14% in the posterior cingulate cortex up 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 first human in vivo evidence for a role of limbic mGlu5 in the pathophysiology of alcohol dependence, possibly involved in a compensatory mechanism helping to reduce craving during abstinence.
Journal: Journal of Nuclear Medicine
ISSN: 0161-5505
Issue: 4
Volume: 59
Pages: 682 - 690
Number of pages: 9
Publication year:2018
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:10
CSS-citation score:4
Authors:International
Authors from:Higher Education
Accessibility:Open