Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Behav Brain Res. 2013 Jan 1;236(1):344-349. doi: 10.1016/j.bbr.2012.09.003. Epub 2012 Sep 12.
By examining the involvement of transient receptor potential vanilloid type 1 (TRPV1) in the stress modulation of learning and memory processes in mice, we evaluated the effects of endovanilloid N-oleoyldopamine (OLDA) on the long-term potentiation (LTP) of the lateral nucleus of the amygdala (LA). After high-frequency stimulation of external capsule fibers we found that LA-LTP is reduced in OLDA-treated slices derived from adult C57BL/6 control mice. The specificity of the TRPV1 receptor activation by OLDA was confirmed by blocking the OLDA-induced inhibitory effect on LA-LTP with the specific TRPV1 receptor antagonist AMG 9810. The specificity of OLDA was further supported by using TRPV1 deficient mice, where the effect of OLDA on LA-LTP was missing. Following exposure to a forced swim test (FST) OLDA enhanced LA-LTP in control but not TRPV1-deficient mice. The results also show that a short period of acute stress significantly impairs LA-LTP. Since we have recently shown the involvement of cannabinoid CB1 receptors in the mediation of capsaicin-induced inhibitory effects on LA-LTP ([23] Zschenderlein et al., 2011), it is reasonable to assume that the OLDA-induced enhancement of LA-LTP after the forced swim test can be attributed to the up-regulation of TRPV1 and the action of ligands such as anandamide on TRPV1. As a result, stimulation of TRPV1 receptors rescues LTP in slices derived from swim-stressed mice.
通过研究瞬时受体电位香草酸亚型 1(TRPV1)在调节学习和记忆过程中的作用,我们评估了内源性大麻素 N-油酰基多巴胺(OLDA)对侧杏仁核(LA)长时程增强(LTP)的影响。在对外部囊纤维进行高频刺激后,我们发现 OLDA 处理的切片中 LA-LTP 减少,这些切片来源于成年 C57BL/6 对照组小鼠。OLDA 对 TRPV1 受体的激活特异性通过使用特异性 TRPV1 受体拮抗剂 AMG 9810 阻断 OLDA 对 LA-LTP 的抑制作用得到证实。OLDA 的特异性进一步通过使用 TRPV1 缺陷型小鼠得到支持,在这种小鼠中,OLDA 对 LA-LTP 的作用缺失。在进行强迫游泳测试(FST)后,OLDA 增强了对照组而非 TRPV1 缺陷型小鼠的 LA-LTP。研究结果还表明,短期急性应激显著损害 LA-LTP。由于我们最近表明大麻素 CB1 受体参与介导辣椒素对 LA-LTP 的抑制作用[23](Zschenderlein 等人,2011 年),因此可以合理地假设,在强迫游泳测试后,OLDA 诱导的 LA-LTP 增强可以归因于 TRPV1 的上调以及内源性大麻素如花生四烯酸酰胺对 TRPV1 的作用。结果,刺激 TRPV1 受体可挽救游泳应激小鼠切片中的 LTP。