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

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العنوان: Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density
المؤلفون: Kroll, Sara L, Hulka, Lea M, Kexel, Ann-Kathrin, Vonmoos, Matthias, Preller, Katrin H, Treyer, Valerie, Ametamey, Simon M, Baumgartner, Markus R, Boost, Carola, Pahlisch, Franziska, Rohleder, Cathrin, Leweke, F Markus, Quednow, Boris B
المصدر: Kroll, Sara L; Hulka, Lea M; Kexel, Ann-Kathrin; Vonmoos, Matthias; Preller, Katrin H; Treyer, Valerie; Ametamey, Simon M; Baumgartner, Markus R; Boost, Carola; Pahlisch, Franziska; Rohleder, Cathrin; Leweke, F Markus; Quednow, Boris B (2023). Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density. Translational Psychiatry, 13(1):325.
بيانات النشر: Nature Publishing Group
سنة النشر: 2023
المجموعة: University of Zurich (UZH): ZORA (Zurich Open Repository and Archive
مصطلحات موضوعية: Clinic for Nuclear Medicine, Clinic for Psychiatry, Psychotherapy, and Psychosomatics, 610 Medicine & health
الوصف: 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 $^{11}$C-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.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 2158-3188
العلاقة: https://www.zora.uzh.ch/id/eprint/238085/1/ZORA238085.pdfTest; info:pmid/37857616; urn:issn:2158-3188
DOI: 10.5167/uzh-238085
DOI: 10.1038/s41398-023-02628-7
الإتاحة: https://doi.org/10.5167/uzh-23808510.1038/s41398-023-02628-7Test
https://www.zora.uzh.ch/id/eprint/238085Test/
https://www.zora.uzh.ch/id/eprint/238085/1/ZORA238085.pdfTest
حقوق: info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.46EAEA02
قاعدة البيانات: BASE
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