Wincewicz Dominik, Braszko Jan J
Department of Clinical Pharmacology, Medical University of Bialystok, Poland
Department of Clinical Pharmacology, Medical University of Bialystok, Poland.
J Renin Angiotensin Aldosterone Syst. 2015 Sep;16(3):495-505. doi: 10.1177/1470320314526269. Epub 2014 Mar 12.
Despite recognition of stress as a causation of severe neuropsychological dysfunctions, no casual and clinically effective anti-stress therapeutic strategy has yet been found. We have previously shown that blockade of initial stress response by angiotensin receptor blockers alleviates the negative effect of prolonged stress on cognitive non-spatial functions of rats. Here we aimed to find whether telmisartan reduces stress-related memory decline in spatial hippocampal-dependent learning tasks conditioned upon differences in level of stress induced by aversive nature of memory tests.
Male Wistar rats were exposed to chronic restraint stress for three weeks and daily treated with either vehicle or telmisartan (1 mg/kg). Afterwards rats were tested in three spatial learning and memory paradigms: Morris water maze (MWM), radial arm maze (RAM), and Barnes maze (BM).
Stressed animals demonstrated significantly impaired performance in all the tests, which was normalized in the animals stressed and treated with telmisartan. Interestingly, despite the fact that MWM and RAM are more stressful, which affects animal behavior, therefore considered less sensitive than BM, more significant effect of telmisartan was found in MWM and RAM than BM.
AT1 angiotensin receptor blockade attenuates negative effect of both acute and chronic stress on spatial memory.
尽管人们认识到应激是严重神经心理功能障碍的一个病因，但尚未找到一种偶然且临床有效的抗应激治疗策略。我们之前已经表明，血管紧张素受体阻滞剂阻断初始应激反应可减轻长期应激对大鼠认知非空间功能的负面影响。在此，我们旨在探究替米沙坦是否能减轻在基于记忆测试的厌恶性质所诱导的应激水平差异而进行的空间海马依赖性学习任务中与应激相关的记忆衰退。
雄性Wistar大鼠暴露于慢性束缚应激三周，每天给予溶剂或替米沙坦（1毫克/千克）治疗。之后，大鼠在三种空间学习和记忆范式中接受测试：莫里斯水迷宫（MWM）、放射状臂迷宫（RAM）和巴恩斯迷宫（BM）。
应激动物在所有测试中的表现均显著受损，而在接受应激并给予替米沙坦治疗的动物中，这种情况得到了正常化。有趣的是，尽管MWM和RAM的应激性更强，会影响动物行为，因此被认为比BM的敏感性更低，但在MWM和RAM中发现替米沙坦的效果比在BM中更显著。
AT1血管紧张素受体阻断可减轻急性和慢性应激对空间记忆的负面影响。
