Alcohol addiction is associated with decreased limbic mGluR5 availability: a 18F-FPEB PET study in human.

15 Objectives Animal studies have demonstrated a critical role of metabotropic glutamate receptor subtype 5 (mGluR5) signaling in the physiopathology of alcohol addiction (1-3), but direct human evidence is lacking. The goal of this study was to investigate cerebral mGluR5 availability in alcohol-dependent subjects in comparison to healthy controls using 18F-FPEB PET imaging. Methods Dynamic 18F-FPEB PET scans (90min) combined with arterial blood sampling were acquired in 16 recently abstinent alcohol-dependent patients (11 smokers; 3F/13M; age 45±8 y, range 32-57 y) and 32 age-matched healthy controls (non-smokers; 14F/18M; age 45±13 y, range 27-65 y). Regional mGluR5 availability was quantified as the 18F-FPEB total distribution volume (VT), using both voxel- and VOI-based analyses in PMOD v3.6, with and without partial volume effect correction (PVC). Alcohol use patterns were determined by self-report questionnaires, and recent alcohol consumption was quantitatively assessed using ethyl glucuronide hair analysis. Results Compared to controls, voxel-wise analysis showed regional decreased mGluR5 availability in alcoholics in the bilateral cingulate, caudate, and insular cortex (Figure; P Conclusions mGluR5 availability is decreased in the limbic system of alcohol-dependent subjects. These data further imply the functional role of mGluR5 in the physiopathology of alcohol addiction, next to recent clinical PET reports on nicotine (4) and cocaine (5) addiction.