腺苷A2A受体基因敲除对小鼠的空间参考记忆和工作记忆的影响

Effect of adenosine A2A receptors gene knock-out on spatial working memory and reference memory in mice

目的观察腺苷A2A受体基因敲除对小鼠空间学习记忆过程的影响，探讨腺苷A2A受体与空间学习记忆的关系及可能的调节机制。方法选用腺苷A2A受体基因敲除小鼠模型（A2ARKO组，n=13）和同窝野生型小鼠（WT组，n=15）。采用Morris水迷宫和八臂迷宫两种实验方法分别检测其空间参考记忆和工作记忆能力。结果腺苷A2A受体基因敲除小鼠在八臂迷宫训练中工作记忆错误数显著少于野生型（RANOVA组间效应：F=146．11，P〈0．01）；在Morris水迷宫重复获得试验中工作记忆成绩显著优于野生型（trial4／trial1指数组间效应：F=6．17，P=0．026），而八臂迷宫训练空间参考记忆错误数（组间效应：F=0．083，P=0．777）及Morris水迷宫定位航行（组间效应：F=2．552，P=0．132）和空间探索试验成绩（A2ARKO：4．50±2．27；WT：2．50±1．93；t=1．901，P=0．078），2组差异无显著性。结论腺苷A2A受体基因敲除小鼠表现为空间工作记忆增强，可见脑内腺苷A2A受体参与空间学习记忆的调节，它对空间工作记忆的影响更为显著。

Objective To investigate the effects and mechanism of adenosine A2A receptors （A2AR）on spatial memory in mice. Methods Mice with adenosine A2A receptors gene knocked out （A2ARKO, n = 13） were compared to their wild type littermates （WT, n = 15）. Eight-arm radial maze and Morris water maze were used to measure their spatial reference memory and spatial working memory. Results Compared to the WT littermates, A2ARKO mice displayed significantly improved working memory in both MWM and radial maze performance. However there was no significant difference in spatial reference memory in MWM test between the A2ARKO mice and WT littermate. Conclusion Genetic inactivation of A2A receptors significantly enhances spatial memory in both MWM and radial maze tests, indicating the important role of adenosine A2A receptors in learning spatial memory in mice. This enhancement of spatial memory is particularly evident for spatial working memory by A2A receptor inactivation.