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血管紧张素受体拮抗剂 losartan 注射到急性应激大鼠杏仁核产生类似抗焦虑的效果。

Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats.

机构信息

Laboratory of Neurosciences and Experimental Psychology, IMBECU-CONICET, Department of Pathology, Faculty of Medical Sciences, National University of Cuyo, Mendoza (5500), Argentina.

出版信息

Pharmacol Rep. 2012;64(1):54-63. doi: 10.1016/s1734-1140(12)70730-2.

Abstract

It has been recognized that the stress-related peptides are involved in anxiety states. Angiotensin II receptor blockade by systemic administration of the AT(1) receptor antagonists has been proposed as a new treatment possibility for anxiety disorders. For better understanding of the related mechanisms, in this study we evaluated effects of bilateral intraamygdaloid injections of 2 (LOS 2) and 4 (LOS 4) μg of losartan (LOS), a selective AT(1) receptor antagonist, on the behavior of the not stressed and acutely stressed rats in an elevated "plus" maze. Under non-stress conditions, LOS 4 increased time spent in the open arms (p < 0.01), number of extreme open arm arrivals (p < 0.05), time per entry (p < 0.01), and the number of total arm entries (p < 0.05) showing thus considerable anxiolytic activity. The open arm extreme arrivals were increased by LOS 4 in both not stressed (p < 0.05) and stressed (p < 0.05) rats. When no stressed and stressed LOS 4 animals were compared, time per entry and the number of closed arm entries (p < 0.05, both) were decreased in the latter group. Moreover, the LOS 4 stressed rats had significantly increased open/closed arm quotient (p < 0.05) as compared to the both control and LOS 4 non-stress group (p < 0.05, both). These findings suggest that the AT(1) receptor blockade in amygdala is important for the anxiolytic action of LOS (and probably other AT(1) receptor blockers) under both non-stress and stress conditions.

摘要

已经认识到,应激相关肽参与焦虑状态。通过全身给予血管紧张素 II 受体拮抗剂 AT(1) 受体拮抗剂的血管紧张素 II 受体阻断被提出作为焦虑障碍的新的治疗可能性。为了更好地理解相关的机制,在这项研究中我们评估了双侧杏仁核内注射 2(LOS 2)和 4(LOS 4)μg 的洛沙坦(LOS),一种选择性 AT(1) 受体拮抗剂,对非应激和急性应激大鼠在高架“+”迷宫中的行为的影响。在非应激条件下,LOS 4 增加了开放臂的时间(p < 0.01),极端开放臂到达的次数(p < 0.05),每次进入的时间(p < 0.01)和总臂进入的次数(p < 0.05),显示出相当的抗焦虑活性。LOS 4 在非应激(p < 0.05)和应激(p < 0.05)大鼠中均增加了开放臂的极端到达次数。当比较非应激和应激的 LOS 4 动物时,后者组的每次进入时间和封闭臂进入次数减少(p < 0.05,两者)。此外,与两个对照组和 LOS 4 非应激组相比,LOS 4 应激大鼠的开放/封闭臂比值显著增加(p < 0.05,两者)。这些发现表明,杏仁核中的 AT(1) 受体阻断对于 LOS(和可能其他 AT(1) 受体阻滞剂)在非应激和应激条件下的抗焦虑作用是重要的。

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