TY - JOUR T1 - Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol Dependence JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 682 LP - 690 DO - 10.2967/jnumed.117.199422 VL - 59 IS - 4 AU - Gil Leurquin-Sterk AU - Jenny Ceccarini AU - Cleo L. Crunelle AU - Bart de Laat AU - Jef Verbeek AU - Stephanie Deman AU - Hugo Neels AU - Guy Bormans AU - Hendrik Peuskens AU - Koen Van Laere Y1 - 2018/04/01 UR - http://jnm.snmjournals.org/content/59/4/682.abstract N2 - 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. ER -