Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
Behav Brain Res. 2013 Sep 1;252:10-7. doi: 10.1016/j.bbr.2013.05.027. Epub 2013 May 25.
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.
内源性大麻素（Anandamide）和 2-花生四烯酸甘油（2-AG）是两种主要的内源性大麻素，通过激活 1 型（CB1r）和 2 型（CB2r）大麻素受体发挥作用。内源性大麻素通过激活特定脑区（包括背外侧导水管周围灰质（dlPAG））中的 CB1r 抑制焦虑样反应。2-AG 也能减轻焦虑样反应，但这些作用的神经解剖部位仍不清楚。在这里，我们假设增强 dlPAG 中的 2-AG 信号会诱导出抗焦虑样作用，并对此进行了验证。同时，我们还研究了涉及的机制。雄性 Wistar 大鼠接受 dlPAG 内注射 2-AG、URB602（2-AG 水解酶，单酰基甘油脂肪酶--MGL 的抑制剂）、AM251（CB1r 拮抗剂）和 AM630（CB2r 拮抗剂）。在以下处理后，在高架十字迷宫中分析行为。实验 1：载体（veh）或 2-AG（5 pmol、50 pmol 和 500 pmol）。实验 2：载体或 URB602（30 pmol、100 pmol 或 300 pmol）。实验 3：载体或 AM251（100 pmol）后载体或 2-AG（50 pmol）。实验 4：载体或 AM630（1000 pmol）后载体或 2-AG。实验 5：载体或 AM251 后载体或 URB602（100 pmol）。实验 6：载体或 AM630 后载体或 URB602。2-AG（50 pmol）和 URB602（100 pmol）显著增加了装置开放臂的探索，表明具有抗焦虑样作用。这些行为反应被 CB1r（AM251）或 CB2r（AM630）拮抗剂所阻断。我们的结果表明，dlPAG 中 2-AG 水平的增加诱导出抗焦虑样作用。该机制似乎涉及 CB1r 和 CB2r 受体。
