Modulation of anxiety-like behavior by the endocannabinoid 2-arachidonoylglycerol (2-AG) in the dorsolateral periaqueductal gray
| Autor: | Ana F. Almeida-Santos, L.C. Rosa, Pedro H. Gobira, Daniele C. Aguiar, Fabrício A. Moreira, Francisco Silveira Guimarães |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
AM251 medicine.medical_specialty Elevated plus maze Indoles Cannabinoid receptor Arachidonic Acids Anxiety URB602 FARMACOLOGIA Periaqueductal gray Glycerides Behavioral Neuroscience chemistry.chemical_compound Piperidines Internal medicine medicine Animals Periaqueductal Gray Rats Wistar Maze Learning Cannabinoid Receptor Antagonists Cannabinoid Receptor Agonists Analysis of Variance Dose-Response Relationship Drug Biphenyl Compounds Antagonist Anandamide Endocannabinoid system Rats Disease Models Animal Endocrinology chemistry Pyrazoles Neuroscience Endocannabinoids medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0166-4328 |
| DOI: | 10.1016/j.bbr.2013.05.027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect