三种腺苷受体拮抗剂对小鼠空间记忆的影响比较

目的：探讨腺苷受体非特异性拮抗剂咖啡因、腺苷A1受体特异性拮抗剂DPCPX及腺苷A24受体特异性拮抗剂SCH58261对小鼠空间记忆的影响。方法：C57BL／6J雄性小鼠65只，分成咖啡因低剂量组（10mg／kg，n=15）、咖啡因高剂量组（50mg／kg，n=15）、DPCPX组（5mg／kg，n=10）、SCH58261组（5mg／kg，n=10）和生理盐水对照组（n=15）。每日4次训练结束后立即腹腔注射给药。用Morris水迷宫检测定位航行的潜伏期和空间探索指标，评价实验动物的空间学习记忆能力。结果：①咖啡因小剂量（10mg／kg）组分别与高剂量（50mg／kg）组和对照组相比，定位航行试验的逃避潜伏期显著缩短，空间搜索试验穿越原平台位置的次数显著增多。②DPCPX和SCH58261对小鼠Morris水迷宫的定位航行试验的潜伏期和空间探索能力无明显影响。结论：腺苷受体非特异性拮抗剂咖啡因小剂量能够提高小鼠的空间学习记忆能力，而单用腺苷A1或A24受体特异性拮抗剂对空间学习记忆并无明显影响，小剂量咖啡因对空间学习记忆的影响可锥存在腺菩以外的调节机制。

Comparison of effects of three kinds of adenosine receptor antagonists on spatial learning and memory in mice tested in the morris water maze

Objectlve： To investigate the effects of adenosine receptors inactivation on spatial memory in mice by non-specific adenosine receptor antagonist caffeine, A1 receptor antagonist DPCPX and A24 receptor antagonist SCH58261. Methods： Sixty-five male C57BL/6J mice were randomly assigned to five groups： caffeine （10 mg/kg）, caffeine （50 mg/kg）, DPCPX （5 mg/kg）, SCH58261 （5 mg/kg） and saline, by intraperitoneal injection right after the completion of the behavioral training. The mice were tested by the escape latencies of place navigation testing and the times of crossing the exact position of the former platform of probe trial testing in Morris water maze （MWM） in which spatial learning and memory were assessed. Results： （1）Mice treated with caffeine at the low dose （10 mg/kg） significantly decreased the escape latencies and increased the times of crossing the exact position of the former platform in MWM, compared to the mice treated with saline. In contrast, mice treated with high doses of caffeine （50 mg/kg） had no effect on improving behavioral performance in MWM test. （2）There was no significant difference in MWM performance between the mice treated with DPCPX or SCH58261 and the mice treated with saline. Conclusion： The non-selective adenosine receptor antagonist caffeine at the low dose （but not high dose） enhances spatial memory in MWM.However, selective A1 or A24 receptor antagonists are ineffective to improve spatial memory, indicating either combined inactivation of A1 or A24 receptor or additional molecular mechanisms are responsible for the memory enhancement bv low doses caffeine.