Modulation of anxiety-like behavior by the endocannabinoid 2-arachidonoylglycerol (2-AG) in the dorsolateral periaqueductal gray
Abstract
Anandamide and 2-arachidonoylglycerol (2-AG) are the two main endocannabinoids, exerting their effects by activating type 1 (CB1r) and type 2 (CB2r) cannabinoid receptors. Anandamide inhibits anxiety-like responses through the activation of CB1r in certain brain regions, including the dorsolateral periaqueductal gray (dlPAG). 2-AG also attenuates anxiety-like responses, although the neuroanatomical sites for these effects remained unclear. Here, we tested the hypothesis that enhancing 2-AG signaling in the dlPAG would induce anxiolytic-like effects. The mechanisms involved were also investigated. Male Wistar rats received intra-dlPAG injections of 2-AG, URB602 (inhibitor of the 2-AG hydrolyzing enzyme, mono-acylglycerol lipase--MGL), AM251 (CB1r antagonist) and AM630 (CB2r antagonist). The behavior was analyzed in the elevated plus maze after the following treatments. Exp. 1: vehicle (veh) or 2-AG (5 pmol, 50 pmol, and 500 pmol). Exp. 2: veh or URB602 (30 pmol, 100 pmol or 300 pmol). Exp. 3: veh or AM251 (100 pmol) followed by veh or 2-AG (50 pmol). Exp. 4: veh or AM630 (1000 pmol) followed by veh or 2-AG. Exp. 5: veh or AM251 followed by veh or URB602 (100 pmol). Exp. 6: veh or AM630 followed by veh or URB602. 2-AG (50 pmol) and URB602 (100 pmol) significantly increased the exploration of the open arms of the apparatus, indicating an anxiolytic-like effect. These behavioral responses were prevented by CB1r (AM251) or CB2r (AM630) antagonists. Our results showed that the augmentation of 2-AG levels in the dlPAG induces anxiolytic-like effects. The mechanism seems to involve both CB1r and CB2r receptors.
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The midbrain periaqueductal gray (PAG) is a region known to regulate defensive behaviors relevant to anxiety.
“a region known to regulate defensive behaviors relevant to anxiety (Bandler and Shipley, 1994; Almeida-Santos et al., 2013).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Almeida-Santos et al., 2013
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- Authors
- Almeida-Santos, A. F., Gobira, P. H., Rosa, L. C., Guimaraes, F. S., Moreira, F. A., & Aguiar, D. C.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- Corresponding author
- Aguiar, D.C.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 252
- Pages
- 10-17
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2045536121
- Cited by
- 41
- References
- 53
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 3 · 2017: 4 · 2016: 3 · 2015: 9 · 2014: 2 · 2013: 2
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- 2-arachidonoylglycerol, endocannabinoids, anxiety-like behavior, dorsolateral periaqueductal gray, CB1 receptor, CB2 receptor, monoacylglycerol lipase inhibition, anxiolytic effects, elevated plus maze, AM251, AM630, anandamide, cannabinoid receptor antagonists
- MeSH terms
- Analysis of Variance, Animals, Anxiety, Arachidonic Acids, Biphenyl Compounds, Disease Models, Animal, Dose-Response Relationship, Drug, Glycerides, Indoles, Male, Periaqueductal Gray, Piperidines, Pyrazoles, Rats, Wistar, Maze Learning, Rats, Cannabinoid Receptor Agonists, Cannabinoid Receptor Antagonists, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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