ArticlePsychopharmacology2025
Enhancement of peripheral fatty acyl ethanolamide signaling prevents stress-induced social avoidance and anxiety-like behaviors in male rats.
Article in Psychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Intestinal colonization of germ-free mice with indole-producing E. coli modulates the central and peripheral endocannabinoidome.Journal of lipid research · 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
- Editorial: Spanning the spectrum of social behavior: towards more translationally relevant animal models.Psychopharmacology · 2025Article
- Effects of pharmacological inhibition of fatty acid amide hydrolase on corticosterone release: a systematic review of preclinical studies.Discover mental health · 2025Review
- Predator odor stress reactivity, alcohol drinking and the endocannabinoid system.Neurobiology of stress · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleExposure to traumatic events can lead to alterations in social and anxiety-related behaviors. Emerging evidence suggests that peripheral host-defense processes are implicated in the expression of stress-induced behavioral responses and may be targeted to mitigate the negative sequalae of stress exposure.
objectivesIn this study, we used the peripherally restricted FAAH inhibitor URB937 to investigate the effects of the fatty acyl ethanolamide (FAE) family of lipid mediators - which include the endocannabinoid anandamide and the endogenous PPAR-α agonists, oleoylethanolamide and palmitoylethanolamide - on behavioral and peripheral biochemical responses to two ethologically distinct rat models of stress.
methodsMale adult rats were exposed to acute social defeat, a model of psychological stress (Experiment 1), or to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a test of innate predator-evoked fear (Experiment 2), and subsequently treated with URB937 (1 or 3 mg/kg, intraperitoneal) or vehicle. Behavioral analyses were conducted 24 h (Experiment 1) or 7 days (Experiment 2) after exposure.
resultsURB937 administration prevented the emergence of both social avoidance behavior after social defeat stress and anxiety-related behaviors after TMT exposure. Further, URB937 administration blocked social defeat-induced transient increase in plasma concentrations of pro-inflammatory cytokines and the elevation in plasma corticosterone levels observed 24 h after social defeat
conclusionsEnhancement of peripheral FAAH-regulated lipid signaling prevents the emergence of stress-induced social avoidance and anxiety-like behaviors in male rats through mechanisms that may involve an attenuation of peripheral cytokine release induced by stress exposure.
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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.