ArticlePsychopharmacology2015
2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Biobehavioral Interactions between Endocannabinoid and Hypothalamicpituitary- adrenal Systems in Psychosis: A Systematic Review.Current neuropharmacology · 2024Pooled it
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Association between BDNF/CB1R expression and postoperative pain and recovery in patients with preoperative sleep disorders.BMC anesthesiology · 2025Article
- 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
- The Interplay of Exogenous Cannabinoid Use on Anandamide and 2-Arachidonoylglycerol in Anxiety: Results from a Quasi-Experimental Ad Libitum Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice.Psychopharmacology · 2024Article
- Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects.iScience · 2024Article
- Cannabinoids and monoaminergic system: implications for learning and memory.Frontiers in neuroscience · 2024Review
- Article
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- Synaptic and cellular endocannabinoid signaling mechanisms regulate stress-induced plasticity of nucleus accumbens somatostatin neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance.Antioxidants (Basel, Switzerland) · 2023Review
- Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance.Neurobiology of stress · 2023Article
- Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review.Behavioural neurology · 2023Review
- Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- The Endocannabinoid 2-Arachidonoylglycerol Bidirectionally Modulates Acute and Protracted Effects of Predator Odor Exposure.Biological psychiatry · 2022Article
- Article
- Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation?Biological psychiatry · 2022Review
- Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition.Cells · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleThe contribution of two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), in the regulation of fear expression is still unknown.
objectivesWe analyzed the role of different players of the endocannabinoid system on the expression of a strong auditory-cued fear memory in male mice by pharmacological means.
resultsThe cannabinoid receptor type 1 (CB1) antagonist SR141716 (3 mg/kg) caused an increase in conditioned freezing upon repeated tone presentation on three consecutive days. The cannabinoid receptor type 2 (CB2) antagonist AM630 (3 mg/kg), in contrast, had opposite effects during the first tone presentation, with no effects of the transient receptor potential vanilloid receptor type 1 (TRPV1) antagonist SB366791 (1 and 3 mg/kg). Administration of the CB2 agonist JWH133 (3 mg/kg) failed to affect the acute freezing response, whereas the CB1 agonist CP55,940 (50 μg/kg) augmented it. The endocannabinoid uptake inhibitor AM404 (3 mg/kg), but not VDM11 (3 mg/kg), reduced the acute freezing response. Its co-administration with SR141716 or SB366791 confirmed an involvement of CB1 and TRPV1. AEA degradation inhibition by URB597 (1 mg/kg) decreased, while 2-AG degradation inhibition by JZL184 (4 and 8 mg/kg) increased freezing response. As revealed in conditional CB1-deficient mutants, CB1 on cortical glutamatergic neurons alleviates whereas CB1 on GABAergic neurons slightly enhances fear expression. Moreover, 2-AG fear-promoting effects depended on CB1 signaling in GABAergic neurons, while an involvement of glutamatergic neurons remained inconclusive due to the high freezing shown by vehicle-treated Glu-CB1-KO.
conclusionsOur findings suggest that increased AEA levels mediate acute fear relief, whereas increased 2-AG levels promote the expression of conditioned fear primarily via CB1 on GABAergic neurons.
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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.