目的 探讨腺苷A2A受体基因敲除、A2A受体激动剂干预或A2A受体抑制剂干预对小鼠运动活性、焦虑和抑郁样行为的影响.方法 取腺苷A2A受体基因敲除(A2AKO)的雄性小鼠(A2AKO组)及同窝野生型(WT)C57BL/6小鼠(WT组)待用.另取雄性清洁级C57BL/6小鼠,随机分为SCH58261组、CGS21680组和对照组,分别给予腺苷A2A受体特异性拮抗剂SCH58261(2mg/kg)、腺苷A2A受体特异性激动剂CGS21680(0.5mg/kg)和同体积(0.25ml)载体溶液(二甲基亚砜+生理盐水)腹膜腔注射,10min后待用.前述各组别小鼠均进行旷场、高架十字迷宫和强迫游泳实验,测定各组小鼠的运动活性、焦虑和抑郁样行为.结果 与WT组比较,A2AKO组旷场总运动路程缩短(P＜0.001),周边区域的滞留时间延长(P＜0.05),进入高架十字迷宫开臂的次数及在开臂滞留时间减少(P＜0.05),强迫游泳的累计不动时间无显著差异(P＞0.05),而CGS21680组旷场总运动路程缩短(P＜0.01),周边区域滞留时间延长(P＜0.01),进入高架十字迷宫开臂的次数及在开臂的滞留时间减少(P＜0.01),强迫游泳的累计不动时间延长(P＜0.001),而SCH58261组旷场总运动路程和中心区域活动路程延长(P＜0.001),强迫游泳的累计不动时间缩短(P＜0.01),高架十字迷宫试验各项指标无显著差异(P＞0.05).结论 腺苷A2A受体激动剂可减少小鼠的自发和探索行为,加重焦虑和抑郁情绪,该效应与腺苷A2A受体基因敲除引发的效应相似,与腺苷A2A受体拮抗剂引发效应相反.%Objective To explore the effects of gene knock-out, agonist or inhibitor of adenosine A2A receptor on the locomotor activity, and anxiety- or depression-like behavior of mice. Methods Male C57BL/6 mice, comprising those underwent gene knock-out of adenosine AjA receptor (AjaKO) and their wild-type (WT) littermates, were assigned into A2A KO group and WT group. Another batch of male C57BL/6, specific-pathogen-free (SPF) mice, were assigned into 9CH58261 group, CGS21680 group and control group. Mice of aforesaid 3 groups were transperitoneally administered with SCH58261, a specific inhibitor of adenosine A2A receptor at a dose of 2mg/kg, CGS21680, a specific agonist of adenosine A2a receptor at a dose of 0. 5mg/kg, and vehicle (0. 25ml, comprising DMSO and saline), respectively. Ten minutes after injection, mice of the 3 groups underwent open-field test, elevated plus-maze test and forced swimming test to detect their locomotor activity, anxiety- and depression-like behavior. Results a) Compared with WT group, the total movement distance decreased (P<0. 001) and the stay time in the peripheral area increased (P<0. 05) in the open-field test, the frequency of entering the open arms and the stay time on the open arms also decreased (P<0. 05) in elevated plus-maze test in the A2a KO group, whereas no significant difference was found between the 2 groups in total immobility time in the forced swimming test (P>0.05). B) Compared with control group, the total movement distance decreased and the stay time in the peripheral area increased significantly in the open field test (P<0. 01), the frequency of entering the open arms and the stay time on the open arms also decreased (P<0. 01) in elevated plus-maze test, and the total immobility time in forced swimming test increased (P<0. 001) in the CGS21680 group, c) Compared with control group, both the total movement distance and the stay time in the peripheral area increased (P<0. 001), the total immobility time in forced swimming test decreased (P<0.01) in SCH58261 group, while no significant difference was found in elevated plus-maze test between the two groups (P>0.05). Conclusions The agonist of adenosine A2A receptor may depress the spontaneous motility and exploratory behavior, and exacerbate the anxiety and depression, and it simulates the effect induced by knock-out of A2A receptor gene, but it is opposite to the effect induced by A2A receptor inhibitor.
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