多巴胺D4受体激动剂ABT-724对注意缺陷多动障碍模型大鼠行为的影响

目的 探讨高选择性多巴胺D4受体激动剂ABT-724对注意缺陷多动障碍(ADHD)动物模型自发性高血压大鼠(SHR)的行为所产生的影响.方法 将哌甲酯(5mg/ks)及三种不同剂量的ABT-724(0.04mg/kg,0.16mg/kg,0.64mg/kg)干预SHR大鼠,并利用开场试验、Morris水迷宫、Làt迷宫对SHR大鼠进行行为学检测,观察SHR大鼠的行为.结果 哌甲酯及ABT-724干预后的SHR大鼠穿越格子数[分别为(70.67±8.59)个,(76.50±10.75)个,(79.17±10.44)个,(65.67±20.62)个]较盐水组大鼠[(130.33±11.40)个]减少,且差异有显著性(P＜0.05)；在Moms水迷宫中,干预后的SHR大鼠空间记忆能力[分别为(52.50±4.04)s,(52.17±2.99)s,(61±8.15)s,(53.83±9.87)s]与盐水组大鼠[(38.83±7.17)s]相比有所提高,差异有统计学意义(P＜0.05)；在Làt迷宫中,干预后的SHR大鼠直立次数[分别为(57.17±5.67)次,(60.83±8.28)次,(55.17±9.45)次,(65.33±9.50)次]与盐水组大鼠[(78.00±13.84)次]相比减少,差异显著(P＜0.05).结论 ABT-724可改善SHR大鼠的自发活动水平、认知功能和非选择性注意力.

Effect of dopamine D4 receptor agonist ABT-724 on behaviors in rat model of attention-deficit hyperactivity disorder

Objective To investigate the effects of a highly selective dopamine D4 receptor (ABT-724)on behaviors in Spontaneously hypertensive rats (SHR),a rat model of attention-deficit hyperactivity disorder (ADHD).Methods After intervention of methylphenidate(5mg/kg) and three different doses of ABT-724(0.04mg/kg,0.16mg/kg,0.64mg/kg),behaviors of SHR were verified by open-field test,Morris water maze and Làt maze.Results Number of square crossing after intervention of methylphenidate and ABT-724 in SHR( 70.67 ± 8.59,76.50 ± 10.75,79.17 ± 10.44,65.67 ± 20.62) was less than the saline control group( 130.33 ± 1 1.40) (P＜0.05).During Morris water maze,SHRs(52.50 ± 4.04,52.17 ± 2.99,61 ± 8.15,53.83 ± 9.87 ) after intervention of both had a better spatial memory ability than control group(38.83 ±7.17) (P＜0.05).In Làt maze,number of rearing after intervention of both in SHRs(57.17 ± 5.67,60.83 ± 8.28,55.17 ± 9.45,65.33 ± 9.50 ) was less than saline control group(78.00 ± 13.84) (P＜0.05).Conclusion ABT-724 could improve behaviors of spontaneous locomotor activity,cognitive ability,non-selective attention in SHR.