Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density

• Verfasst von: Kroll, Sara Liane [VerfasserIn]
• Verfasst von: Hulka, Lea M. [VerfasserIn]
• Verfasst von: Kexel, Ann-Kathrin [VerfasserIn]
• Verfasst von: Vonmoos, Matthias [VerfasserIn]
• Verfasst von: Preller, Katrin H. [VerfasserIn]
• Verfasst von: Treyer, Valerie [VerfasserIn]
• Verfasst von: Ametamey, Simon M. [VerfasserIn]
• Verfasst von: Baumgartner, Markus R. [VerfasserIn]
• Verfasst von: Boost, Carola [VerfasserIn]
• Verfasst von: Pahlisch, Franziska [VerfasserIn]
• Verfasst von: Rohleder, Cathrin [VerfasserIn]
• Verfasst von: Leweke, F. Markus [VerfasserIn]
• Verfasst von: Quednow, Boris B. [VerfasserIn]
• Titel: Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density
• Verf.angabe: Sara L. Kroll, Lea M. Hulka, Ann-Kathrin Kexel, Matthias Vonmoos, Katrin H. Preller, Valerie Treyer, Simon M. Ametamey, Markus R. Baumgartner, Carola Boost, Franziska Pahlisch, Cathrin Rohleder, F. Markus Leweke and Boris B. Quednow
• E-Jahr: 2023
• Jahr: 19 October 2023
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 18.09.2024
• Titel Quelle: Enthalten in: Translational Psychiatry
• Ort Quelle: London : Nature Publishing Group, 2011
• Jahr Quelle: 2023
• Band/Heft Quelle: 13(2023), 1, Seite 1-10
• ISSN Quelle: 2158-3188
• DOI: doi:10.1038/s41398-023-02628-7
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Addiction
• Sach-SW: Molecular neuroscience
• K10plus-PPN: 1902914635

Abstract

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N = 103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N = 92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N = 33; controls: N = 43). In an additional analysis using 11C-ABP688 positron emission tomography (PET) in a male subsample (CU: N = 18; controls: N = 16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence.