Jenny Ceccarini1,2, Gil Leurquin-Sterk3,2, Cleo Lina Crunelle4,5, Bart de Laat3,2,6, Guy Bormans7, Hendrik Peuskens8,9, Koen Van Laere3,2,6. 1. Department of Nuclear Medicine and Molecular Imaging, UZ Leuven, Leuven, Belgium jenny.ceccarini@uzleuven.be. 2. Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 3. Department of Nuclear Medicine and Molecular Imaging, UZ Leuven, Leuven, Belgium. 4. Toxicological Center, University of Antwerp, Wilrijk, Belgium. 5. Department of Psychiatry, Universitair Ziekenhuis Brussel, Brussels, Belgium. 6. MoSAIC, Molecular Small Animal Imaging Center, KU Leuven, Leuven, Belgium. 7. Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium. 8. University Psychiatric Center, KU Leuven, Kortenberg, Belgium; and. 9. Kliniek Broeders Alexianen, Tienen, Belgium.
Abstract
Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular, cerebral metabotropic glutamate receptor 5 (mGluR5). 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET has revealed that chronic alcohol use leads to decreased limbic mGluR5 availability, which was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2 and 6 mo of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse. Methods: 18F-FPEB scans were performed for 16 recently detoxified alcohol-dependent patients (baseline condition), 2 mo after detoxification (n = 10), and 6 mo after detoxification (n = 8); 32 age- and sex-matched controls were included for comparison. mGluR5 availability was quantified by the 18F-FPEB total distribution volume using both voxel-by-voxel and volume-of-interest analyses. During follow-up, craving was assessed using the Desire for Alcohol Questionnaire, and alcohol consumption was assessed using the timeline follow-back method and monitored by hair ethyl glucuronide analysis. Results: During abstinence, alcohol-dependent patients showed sustained recovered mGluR5 availability in cortical and subcortical regions compared with the baseline, up to the levels observed in controls, after 6 mo in most areas except for the hippocampus, nucleus accumbens, and thalamus. Higher striatopallidal mGluR5 availability was observed at the baseline in patients who had a relapse during the 6-mo follow-up period (+25.1%). Also, normalization of striatal mGluR5 to control levels was associated with reduced craving ("desire and intention to drink" and "negative reinforcement"; r = 0.72-0.94). Conclusion: Reduced cerebral mGluR5 availability in alcohol-dependent patients recovers during abstinence and is associated with reduced craving. Higher striatal mGluR5 availability in alcohol-dependent users may be associated with long-term relapse.
Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular, cerebral metabotropic glutamate receptor 5 (mGluR5). 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET has revealed that chronic alcohol use leads to decreased limbic mGluR5 availability, which was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2 and 6 mo of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse. Methods: 18F-FPEB scans were performed for 16 recently detoxified alcohol-dependent patients (baseline condition), 2 mo after detoxification (n = 10), and 6 mo after detoxification (n = 8); 32 age- and sex-matched controls were included for comparison. mGluR5 availability was quantified by the 18F-FPEB total distribution volume using both voxel-by-voxel and volume-of-interest analyses. During follow-up, craving was assessed using the Desire for Alcohol Questionnaire, and alcohol consumption was assessed using the timeline follow-back method and monitored by hair ethyl glucuronide analysis. Results: During abstinence, alcohol-dependent patients showed sustained recovered mGluR5 availability in cortical and subcortical regions compared with the baseline, up to the levels observed in controls, after 6 mo in most areas except for the hippocampus, nucleus accumbens, and thalamus. Higher striatopallidal mGluR5 availability was observed at the baseline in patients who had a relapse during the 6-mo follow-up period (+25.1%). Also, normalization of striatal mGluR5 to control levels was associated with reduced craving ("desire and intention to drink" and "negative reinforcement"; r = 0.72-0.94). Conclusion: Reduced cerebral mGluR5 availability in alcohol-dependent patients recovers during abstinence and is associated with reduced craving. Higher striatal mGluR5 availability in alcohol-dependent users may be associated with long-term relapse.
Authors: H W Müller-Gärtner; J M Links; J L Prince; R N Bryan; E McVeigh; J P Leal; C Davatzikos; J J Frost Journal: J Cereb Blood Flow Metab Date: 1992-07 Impact factor: 6.200
Authors: Richard M Cleva; Megan P Hicks; Justin T Gass; Kelly C Wischerath; Elizabeth T Plasters; John J Widholm; M Foster Olive Journal: Behav Neurosci Date: 2011-02 Impact factor: 1.912
Authors: Cleo L Crunelle; Michel Yegles; Alexander L N van Nuijs; Adrian Covaci; Mireille De Doncker; Kristof E Maudens; Bernard Sabbe; Geert Dom; Willy E Lambert; Peter Michielsen; Hugo Neels Journal: Drug Alcohol Depend Date: 2013-10-30 Impact factor: 4.492
Authors: Gil Leurquin-Sterk; Andrey Postnov; Bart de Laat; Cindy Casteels; Sofie Celen; Cleo L Crunelle; Guy Bormans; Michel Koole; Koen Van Laere Journal: Synapse Date: 2016-02-08 Impact factor: 2.562
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: 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
Authors: Nathan D Winters; Gaurav Bedse; Anastasia A Astafyev; Toni A Patrick; Megan Altemus; Amanda J Morgan; Snigdha Mukerjee; Keenan D Johnson; Vikrant R Mahajan; Md Jashim Uddin; Philip J Kingsley; Samuel W Centanni; Cody A Siciliano; David C Samuels; Lawrence J Marnett; Danny G Winder; Sachin Patel Journal: J Clin Invest Date: 2021-07-22 Impact factor: 14.808