PT  - JOURNAL ARTICLE
AU  - Leurquin-Sterk, Gil
AU  - Ceccarini, Jenny
AU  - Crunelle, Cleo L.
AU  - de Laat, Bart
AU  - Verbeek, Jef
AU  - Deman, Stephanie
AU  - Neels, Hugo
AU  - Bormans, Guy
AU  - Peuskens, Hendrik
AU  - Van Laere, Koen
TI  - Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol Dependence
AID  - 10.2967/jnumed.117.199422
DP  - 2018 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 682--690
VI  - 59
IP  - 4
4099  - http://jnm.snmjournals.org/content/59/4/682.short
4100  - http://jnm.snmjournals.org/content/59/4/682.full
SO  - J Nucl Med2018 Apr 01; 59
AB  - 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 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET. Methods: Dynamic 90-min 18F-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 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 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.