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oai:repisalud.isciii.es:20.500.12105/183702024-11-28T14:50:19Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Pavón, Francisco Javier author Polis, Ilham Y. author Stouffer, David G. author Cravatt, Benjamin F. author Roberto, Marisa author Martin-Fardon, Rémi author Rodríguez de Fonseca, Fernando author Parsons, Loren H. author Serrano, Antonia authoraffiliation [Pavón,FJ; Polis,IY; Stouffer,DG; Roberto,M; Martin-Fardon,R; Parsons,LH; Serrano,A] Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. [Pavón,FJ; Rodríguez de Fonseca,F; Serrano,A] Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Pavón,FJ] CIBERCV-Instituto de Salud Carlos III and Unidad de Gestión Clínica del Corazón, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Cravatt,BF] Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. 2024-02-19T15:28:40Z 2024-02-19T15:28:40Z 2021-06-09 10.1016/j.ynstr.2021.100293 2352-2895 Neurobiology Of Stress http://hdl.handle.net/10668/3827 33490317 http://hdl.handle.net/20.500.12105/18370 The endocannabinoid system is involved in the regulation of the stress response, but the relative contribution of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) and their mechanisms have to be elucidated. In this study, we compared the effects of the pharmacological inhibition of the two major endocannabinoid-degrading enzymes [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) for AEA and 2-AG, respectively] on stress-coping [forced swim test (FST) and tail suspension test (TST)] and anxiety-like [elevated-plus maze (EPM) and light-dark test (LDT)] behaviors in wild-type and FAAH knockout mice. In vivo microdialysis estimated the effects of FAAH and MAGL inhibition on dopamine (DA) and serotonin (5-HT) levels in the medial prefrontal cortex (mPFC) during an FST. Mice were treated with PF-3845 (FAAH inhibitor), JZL184 (MAGL inhibitor), JZL195 (dual FAAH/MAGL inhibitor) or vehicle. Our data showed that PF-3845 increased latency to immobility and decreased total immobility time in FST, but no effects were observed in TST compared with vehicle-treated wild-type mice. By contrast, JZL184 decreased latency and increased immobility in TST and FST. JZL195 in wild-type mice and JZL184 in FAAH knockout mice reproduced the same passive coping behaviors as JZL184 in wild-type mice in TST and FST. In the microdialysis experiment, FST was associated with increased DA and 5-HT levels in the mPFC. However, JZL184-treated wild-type mice displayed a significant attenuation of forced swim stress-induced DA release compared with vehicle-treated wild-type mice and PF-3845-treated wild-type mice. Finally, FAAH and/or MAGL inhibitors induced robust and consistent anxiolytic-like effects in EPM and LDT. These results suggested differences between FAAH and MAGL inhibition in stress-coping behaviors. Notably, MAGL inhibition induced a consistent avoidant coping behavior and attenuated the stress-induced mPFC DA response in FST. However, more investigation is needed to elucidate the functional association between DA and 2-AG signaling pathways, and the molecular mechanism in the regulation of passive coping strategies during inescapable stress. eng 2-Arachidonoylglycerol Stress-coping behavior Dopamine Mouse Microdialysis Dopamina Ratones Microdiálisis Selective inhibition of monoacylglycerol lipase is associated with passive coping behavior and attenuation of stress-induced dopamine release in the medial prefrontal cortex research article