胍丁胺对生理及应激状态下小鼠空间参考记忆的影响

Effects of agmatine on spatial reference memory of mice under normal and stress conditions

目的研究胍丁胺对生理及应激状态下小鼠空间参考记忆形成及提取的影响。方法采用Morris水迷宫隐蔽平台实验范式研究胍丁胺对小鼠生理和应激状态下空间参考记忆的形成及提取的影响。应激处理:每天隐蔽平台训练(共5 d)前分别施与束缚2 h+不可预知尾部电击、天敌暴露2 h、不可预知足底电击+噪声、转棒运动疲劳1 h、束缚2 h+噪声;探查测试前施与束缚2 h+不可预知尾部电击。酶联免疫吸附法测定小鼠血浆皮质酮浓度。结果生理状态下,与正常对照组相比,隐蔽平台训练前给予胍丁胺(3~30 mg/kg,ig)小鼠逃避潜伏期呈剂量依赖性缩短,其中胍丁胺30 mg/kg组有显著性差异(P<0.05);探查测试前给予胍丁胺(30 mg/kg,ig)小鼠在平台所在目标象限的停留时间及探查距离显著提高(P<0.05)。在应激状态下,训练前急性应激处理有增加小鼠逃避潜伏期的趋势,胍丁胺(30 mg/kg,ig)组小鼠应激状态下小鼠逃避潜伏期显著降低(P<0.05);探查测试前急性应激处理小鼠在平台所在目标象限的停留时间及游泳距离显著降低(P<0.05),应激前给予胍丁胺具有提高小鼠探查测试表现的趋势。应激处理提高小鼠血浆皮质酮水平,给予胍丁胺(3~30 mg/kg,ig)不能降低应激所致小鼠血浆皮质酮水平的升高(P>0.05)。结论胍丁胺增强生理状态下小鼠空间参考记忆的形成和提取;急性应激刺激呈现下调小鼠空间参考记忆形成的趋势、并抑制其提取,但具有改善急性应激状态下空间参考记忆能力下降的趋势。

Objective To study the effects of exogenous agmatine on the formation and retrieval of spatial reference memory of mice under normal and stress conditions.Methods In the Morris Water Maze hidden platform experiment,the effects of agmatine on the formation and retrieval of spatial reference memory of mice under normal and stress conditions were investigated.Before the Mor⁃ris Water Maze hidden platform training(a total of five days),the 2 h restraint+unpredictable tail shock,predator exposure for 2 h,unpredictable foot shock+noise,rotarod exercise fatigue for 1 h,and restraint for 2 h+noise were applied respectively each day.Be⁃fore the probe trial,the 2 h restraint+unpredictable tail shock was applied.Enzyme-linked immunosorbent assay(ELISA)was used to determine the plasma corticosterone concentration in mice.Results Under normal physiological condition,agmatine(3-30 mg/kg,ig)before Morris Water Maze hidden platform training had dose-dependent effects on escape latency,and agmatine(30 mg/kg,ig)significantly shortened the escape latency of mice compared with the control group(P<0.05),significantly improved the residence time and exploration distance of mice in the target quadrant where the platform was located(P<0.05).Acute stress treatment before hidden platform training had a tendency to increase the escape latency of mice.Agmatine(30 mg/kg,ig)significantly reduced the es⁃cape latency of mice under stress conditions(P<0.05).Acute stress treatment before probe trial significantly reduced the residence time and exploration distance of mice in the target quadrant where the platform was located(P<0.05).The administration of agmatine before stress had a tendency to improve the performance of mice in probe trial.Stress treatment increased plasma corticosterone levels in mice,and agmatine(3-30 mg/kg,ig)did not reduce stress-induced plasma corticosterone levels in mice(P>0.05).Conclusion Agmatine promotes the formation and retrieval of spatial reference memory of mice under normal physiological condition.Acute stress leads to a decline in the formation of spatial reference memory of mice and impairs its retrieval,but agmatine tends to reverse the de⁃cline of spatial reference memory ability caused by acute stress.