ArticleBiological psychiatry2022
The Endocannabinoid 2-Arachidonoylglycerol Bidirectionally Modulates Acute and Protracted Effects of Predator Odor Exposure.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Cannabinoid modulation of central amygdala population dynamics during threat investigation.Nature communications · 2026Article
- A Neurotensin Brake on Exploratory Drive under Persistent Threat.bioRxiv : the preprint server for biology · 2026Article
- CB1 receptor signaling at the cingulate-striatal circuit is anxiogenic.Nature communications · 2026Article
- Endocannabinoid modulation of defensive state transitions to innate and learned threat.Psychopharmacology · 2026Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Understanding the Role of Endocannabinoids in Posttraumatic Stress Disorder.International journal of molecular sciences · 2025Review
- Endocannabinoids disinhibit the ventral tegmental nucleus of Gudden to dorsal premammillary nucleus pathway to enhance escape behavior following learned threat experience.Nature communications · 2025Article
- Predator odor stress reactivity, alcohol drinking and the endocannabinoid system.Neurobiology of stress · 2024Article
- Endocannabinoid release at ventral hippocampal-amygdala synapses regulates stress-induced behavioral adaptation.Cell reports · 2023Article
- Article
- Opposing retrograde and astrocyte-dependent endocannabinoid signaling mechanisms regulate lateral habenula synaptic transmission.Cell reports · 2023Article
- Effects of glycogen synthase kinase-3β activity inhibition on cognitive, behavioral, and hippocampal ultrastructural deficits in adulthood associated with adolescent methamphetamine exposure.Frontiers in molecular neuroscience · 2023Article
- Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance.Neurobiology of stress · 2023Article
- Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundStress-related disorders are among the most prevalent psychiatric disorders, characterized by excess fear and enhanced avoidance of trauma triggers. Elucidating the mechanisms regulating temporally distinct aspects of innate and conditioned fear responses could facilitate novel therapeutic development for stress-related disorders. One potential target that has recently emerged is the endocannabinoid system, which has been reported to mediate the physiological response to stress and represents an important substrate underlying individual differences in stress susceptibility.
methodsHere, we exposed male and female CD-1 mice to an innate predator stressor, 2MT (2-methyl-2-thiazoline), to investigate the ability of endocannabinoid signaling to modulate temporally distinct innate and conditioned fear behaviors.
resultsWe found that 2MT exposure increased amygdala 2-AG (2-arachidonoylglycerol) content and selectively increased excitability in central, but not basolateral, amygdala neurons. We also found that pharmacological 2-AG augmentation during stress exposure exacerbated both acute freezing responses and central amygdala hyperexcitability via cannabinoid receptor type 1- and type 2-dependent mechanisms. Finally, 2-AG augmentation during stress exposure reduced long-term contextual conditioned freezing, and 2-AG augmentation 24 hours after stress exposure reduced conditioned avoidance behavior.
conclusionsOur findings demonstrate a bidirectional effect of 2-AG augmentation on innate and conditioned fear behavior, with enhancement of 2-AG levels during stress promoting innate fear responses but ultimately resulting in long-term conditioned fear reduction. These data could reconcile contradictory data on the role of 2-AG in the regulation of innate and conditioned fear-related behavioral responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.