注意缺陷障碍动物模型的行为学特征检测

Behavioral characteristics of animal models of attention deficit hyperactivity disorder

目的:以国外常用的注意缺陷障碍动物模型SHR大鼠为观察对象,观察注意缺陷障碍动物模型的行为学特征。方法:实验于2003-12/2004-01在南京医科大学动物实验中心完成,清洁级SHR大鼠(注意缺陷障碍组)和WKY大鼠(对照组)各10只,鼠龄4周,均为雄性,体质量70～90g,两组之间差异不显著。利用开场试验观察记录大鼠穿越的格子数、大鼠直立次数、理毛次数,以及粪便数,làt迷宫观察大鼠穿越角落的频数及直立和斜搭在墙上的频率,跳台试验记录每只大鼠受到电击后跳上平台的次数,以此作为学习成绩。24h后重新测试,在铜栅通电的情况下,直接将大鼠置于橡皮台上,记录第1次跳下橡皮台的潜伏期和5min内的错误次数作为记忆的成绩。结果:10只SHR大鼠和10只WKY大鼠均进入结果分析。①白天及夜晚开场中SHR大鼠穿越格数及直立次数均较对照组WKY大鼠显著增多(白天:72.10±15.44,37.50±9.59,29.40±15.19,10.30±8.55;夜晚:83.70±11.78,49.00±7.94,42.00±18.12,14.10±10.45,P<0.001)。②SHR大鼠在Làt迷宫中30min内,穿越角落频数、直立次数、理毛次数均较对照组WKY大鼠显著增加(128.30±29.38,151.90±46.51,14.00±5.03;46.10±22.97,36.00±26.31,7.90±4.12,P<0.001或P<0.05);将其分为0～10min,10～20min、20～30min3个时间段来分析,发现随着时间的延续,SHR和WKY大鼠穿越角落频数逐渐减少,但各个时间段内SHR大鼠穿越角落频数仍较对照组WKY大鼠显著增加(63.80±15.5,36.10±13.34,28.40±8.34;26.40±11.01,13.30±12.18,6.40±4.97,t=6.13,3.99,7.15,P均<0.01),SHR和WKY大鼠直立次数随着时间的延续也逐渐减少,但各个时间段内SHR大鼠直立次数仍较对照组WKY大鼠多(67.30±20.49,46.60±21.58,38.00±14.31;18.80±12.04,11.60±12.21,5.60±4.38,t或t’=6.41,4.46,6.85,P均<0.01)。③跳台实验结果显示,SHR和WKY的学习能力差异无显著性,记忆测试时SHR大鼠的潜伏期与WKY大鼠也未见显著差别,但SHR大鼠的错误次数显著高于WKY大鼠(1.42±1.00,0.56±0.73,t=2.19,P<0.05)。结论:利用开场实验、Làt迷宫及跳台实验等多方法结合,可以简单有效的从多动、注意障碍、学习记忆等方面对注意缺陷障碍模型进行行为学检测。

AIM; To observe the behavioral characteristics of animal models of attention deficit hyperactivity disorder （ADHD） with the subjects of SHR rats, a kind of animal model often used in foreign, METHODS： The experiment was carried out in the Animal Experiment Center of Nanjing Medical University from December 2003 to January 2004. Ten clean grade SHR were selected as ADHD group and ten WKY rats were selected as control group, The rats were male ones and aged 4 weeks, 70-90 g; no difference was found between the two groups, The panels the rats passed, the times of straighten and grooming, and times of dejecture were observed and recorded by using open-field environment test; the Lat maze was adopted to observe the frequency of rats passing the comer, frequency of straightening and inclined to wall; and the step-down test was used to record the times of rats to jump to the platform after electric stress. All the data served as study achievement. The tests were performed again 24 hours later： With electric current, the rats were put on the rubber platform to record the latency of first jumping down the platform and number of errors in 5 minutes as the memory achievement. RESULTS： Ten SHR and ten WKY rats were all involved in the result analysis. ①In the open-field environment test, the panels passed and the times of straightening at daytime and night of SHR rats were more than the WKY rats （daytime： 72.10±15.44, 37.50±9.59, 29.40±15.19, 10,30±8.55; night： 83.70±11.78, 49.00±7.94, 42.00±18.12, 14.10±10.45, P 〈 0.001）. ②In the Lat maze the frequency of running across the corners and the times of straightening and grooming in 30 minutes of the SHR rats were significantly increased compared with the WKY rats （128.30±29.38, 151.90±46.51, 14.00±5,03; 46.10±22.97, 36.00±26.31, 7.90±4.12, P 〈 0.01 or P 〈 0.05）; if the 30 minutes were divided into three consecutive 10 minutes, the frequency of running across the corners of SHR and WKY rats was decreased with time, but the frequency of SHR rats were still higher than the WKY rats （63.80±15.5, 36.10±13.34, 28.40±8.34; 26.40±11.01, 13.30±12.18, 6.40±4.97, t=6.13, 3.99, 7.15, P 〈 0.01）; the times of straightening were also decreased with time, and the times of SHR rats were also higher than the WKY rats （67.30±20.49, 46.60±21.58, 38.00±14.31; 18.80±12.04, 11.60±12.21, 5.60±4.38, t or t＇=6.41, 4.46, 6.85, P 〈 0.01）. ③In step down test, there was no significant difference in acquisition between the SHR and WKY groups, so was the latency in memory test; but the number of errors of SHR rats were higher than the WKY rats （1.42±1.00,0.56±0.73, t=2.19, P 〈 0.05）. CONCLUSION： The open-field environment test combined with Lat maze and step down test can detect the behavior characteristics of the animal models of ADHD from hyperactivity, disturbance of attention and learning difficulty.