Cited by 41Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Modulation of anxiety-like behavior by the endocannabinoid 2-arachidonoylglycerol (2-AG) in the dorsolateral periaqueductal gray

Almeida-Santos, A.F., Gobira, P.H., Rosa, L.C., Guimaraes, F.S., Moreira, F.A., Aguiar, D.C.·2013·Behavioural Brain Research

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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Crossref · 10.1016/j.bbr.2013.05.027

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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

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