腺苷A_(2A)受体对小鼠精神运动和情绪行为的调控作用

Regulatory effects of adenosine A_(2A) receptors on psychomotor ability and mood behavior of mice

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 A2A receptor（A2AKO） and their wild-type（WT） littermates,were assigned into A2AKO group and WT group.Another batch of male C57BL/6,specific-pathogen-free（SPF） mice,were assigned into SCH58261 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 A2AKO 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.