Gil Leurquin-Sterk1, Jenny Ceccarini2, Cleo L Crunelle3,4, Bart de Laat1,5, Jef Verbeek6, Stephanie Deman7, Hugo Neels3, Guy Bormans8, Hendrik Peuskens9, Koen Van Laere1,5. 1. Division of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 2. Division of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium jenny.ceccarini@uzleuven.be. 3. Toxicological Center, University of Antwerp, Wilrijk, Belgium. 4. Department of Psychiatry, University Hospital Brussels, Brussels, Belgium. 5. MoSAIC: Molecular Small Animal Imaging Center, KU Leuven, Leuven, Belgium. 6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands. 7. Genomics Core, UZ Leuven, and Department of Human Genetics, KU Leuven, Leuven, Belgium. 8. Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium; and. 9. University Psychiatric Center, KU Leuven, Kortenberg, and Kliniek Broeders Alexianen, Tienen, Belgium.
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 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.
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.
Authors: Carolina L Haass-Koffler; Roberta Perciballi; Molly Magill; Antonella Loche; Roberto Cacciaglia; Lorenzo Leggio; Robert M Swift Journal: Psychopharmacology (Berl) Date: 2021-11-03 Impact factor: 4.530
Authors: Kelly Smart; Patrick D Worhunsky; Dustin Scheinost; Gustavo A Angarita; Irina Esterlis; Richard E Carson; John H Krystal; Stephanie S O'Malley; Kelly P Cosgrove; Ansel T Hillmer Journal: Alcohol Clin Exp Res Date: 2022-04-21 Impact factor: 3.928
Authors: Jenny Ceccarini; Gil Leurquin-Sterk; Cleo Lina Crunelle; Bart de Laat; Guy Bormans; Hendrik Peuskens; Koen Van Laere Journal: J Nucl Med Date: 2019-09-03 Impact factor: 10.057
Authors: Ansel T Hillmer; Gustavo A Angarita; Irina Esterlis; Jon Mikael Anderson; Nabeel Nabulsi; Keunpoong Lim; Jim Ropchan; Richard E Carson; John H Krystal; Stephanie S O' Malley; Kelly P Cosgrove Journal: Neuropsychopharmacology Date: 2020-09-12 Impact factor: 7.853