Publication: Selective inhibition of monoacylglycerol lipase is associated with passive coping behavior and attenuation of stress-induced dopamine release in the medial prefrontal cortex
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Identifiers
Date
2021-06-09
Authors
Pavón, Francisco Javier
Polis, Ilham Y.
Stouffer, David G.
Cravatt, Benjamin F.
Roberto, Marisa
Martin-Fardon, Rémi
Rodríguez de Fonseca, Fernando
Parsons, Loren H.
Serrano, Antonia
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
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.
Description
MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Monoacylglycerol Lipases
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Endocannabinoids
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators::Autacoids::Serotonin
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Central Nervous System Depressants::Tranquilizing Agents::Anti-Anxiety Agents
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immobilization::Restraint, Physical::Hindlimb Suspension
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Adaptation, Psychological
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Frontal Lobe::Prefrontal Cortex
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Monoacylglycerol Lipases
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Endocannabinoids
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators::Autacoids::Serotonin
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Central Nervous System Depressants::Tranquilizing Agents::Anti-Anxiety Agents
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immobilization::Restraint, Physical::Hindlimb Suspension
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Adaptation, Psychological
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Frontal Lobe::Prefrontal Cortex
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety
DeCS Terms
CIE Terms
Keywords
2-Arachidonoylglycerol, Stress-coping behavior, Dopamine, Mouse, Microdialysis, Dopamina, Ratones, Microdiálisis
Citation
Pavón FJ, Polis IY, Stouffer DG, Cravatt BF, Roberto M, Martin-Fardon R, et al. Selective inhibition of monoacylglycerol lipase is associated with passive coping behavior and attenuation of stress-induced dopamine release in the medial prefrontal cortex. Neurobiol Stress. 2021 Jan 9;14:100293