ArticleBiological psychiatry2016
Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression.Nature human behaviour · 2025Pooled it
- Birth, cognitive and behavioral effects of intrauterine cannabis exposure in infants and children: A systematic review and meta-analysis.Addiction (Abingdon, England) · 2024Pooled it
- Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.Psychoneuroendocrinology · 2021Trial
- Sterol carrier protein 2 loss reduces anxiety and enhances fear extinction.Journal of affective disorders · 2026Article
- CB1 receptor signaling at the cingulate-striatal circuit is anxiogenic.Nature communications · 2026Article
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- An Amygdala-hippocampus Circuit for Endocannabinoid Modulation of Anxiety Avoidance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Brain region specific regulation of anandamide (down) and sphingosine-1-phosphate (up) in association with anxiety (AEA) and resilience (S1P) in a mouse model of chronic unpredictable mild stress.Pflugers Archiv : European journal of physiology · 2024Article
- Identification of DAGLA as an autoantibody target in cerebellar ataxia.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- How depression and antidepressant drugs affect endocannabinoid system?-review of clinical and preclinical studies.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice.Psychopharmacology · 2024Article
- AstrocyticCannabis and cannabinoid research · 2024Article
- Early life stress induces decreased expression of CB1R and FAAH and epigenetic changes in the medial prefrontal cortex of male rats.Frontiers in cellular neuroscience · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- A Sexually Dimorphic Role for Intestinal Cannabinoid Receptor Subtype-1 in the Behavioral Expression of Anxiety.Cannabis and cannabinoid research · 2023Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDisruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice. The two main endogenous cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on demand from phospholipids. The pathways and enzymes involved in endocannabinoid biosynthesis thus play a major role in regulating the activity of this system. This study investigates the role of the main 2-AG producing enzyme diacylglycerol lipase α (DAGL-α).
methodsWe generated and used knockout mice lacking DAGL-α (Dagla(-/-)) to assess the behavioral consequences of reduced endocannabinoid levels in the brain. We performed different behavior tests to determine anxiety- and depression-related behavioral changes in Dagla(-/-) mice. We also analyzed expression of genes related to the endocannabinoid system via real-time polymerase chain reaction and used the mitotic marker 5-bromo-2'-deoxyuridine to analyze adult neurogenesis.
resultsDagla(-/-) animals show an 80% reduction of brain 2-AG levels but also a reduction in cortical and amygdalar anandamide. The behavioral changes induced by Dagla deletion include a reduced exploration of the central area of the open field, a maternal neglect behavior, a fear extinction deficit, increased behavioral despair, increased anxiety-related behaviors in the light/dark box, and reduced hippocampal neurogenesis. Some of these behavioral changes resemble those observed in animals lacking the CB1 receptor.
conclusionsOur findings demonstrate that the deletion of Dagla adversely affects the emotional state of animals and results in enhanced anxiety, stress, and fear responses.
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Registered trials
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.