氟哌啶醇对MK-801致小鼠高活动性与前脉冲抑制损害的作用☆

Effects of haloperidol on MK-801-induced hyperlocomotion and deficits of prepulse inhibition in mice.

目的观察氟哌啶醇对谷氨酸功能低下小鼠模型表现出的高活动性及前脉冲抑制（prepulse inhibition，PPI）损害的作用。方法昆明种小鼠152只分组（n=8或n=10）进行下述对照观察：观察不同剂量氟哌啶醇（0．03、0．1、0．3mg／kg）腹腔注射对昆明种小鼠探究行为和自主活动的影响；以0．25mg／kgMK-801诱导小鼠自主活动增加，观察上述剂量氟哌啶醇对MK-801致小鼠高活动性的影响；以0．5mg／kgMK-801诱导小鼠PPI损害，观察氟哌啶醇（0．1、0．3、1mg／kg）对基线水平PPI以及MK-801损害后PPI的作用。结果与对照组比较，氟哌啶醇剂量为0．1mg/kg和0．3mg／kg时，小鼠的探究行为及自主活动总路程减少（P〈0．05）；但剂量为0．03mg／kg时，对小鼠的探究行为及自主活动均无影响（P〉0．05）。氟哌啶醇剂量为0．1—0．3mg／kg时，呈剂量依赖性抑制由MK一801引起的自主活动增加（F=27．23，P〈0．01），0．1mg／kg的氟哌啶醇的抑制程度为22％（P〈0．01），0．3mg,／kg的氟哌啶醇的抑制程度为65％（P〈0．001）。氟哌啶醇（0．1、0．3、1mg／kg）呈剂量依赖性增强了基线的PPI（F=9．06，P〈0．001），增加程度分别为44％（P〈0．05）、60％（P=0．001）和61％（P=0．001）。只有剂量为1mg／kg时抑制了MK-801引起的PPI损害（P〈0．05）。结论氟哌啶醇非特异性地抑制了谷氨酸功能低下小鼠模型表现出的高活动性与PPI损害。

Objective To investigate the effects of haloperidol on hyperlocomotion and deficient prepulse inhibition （PPI） in MK-801 induced hypoglutamatergic schizophrenia model in mice. Methods One hundred fifiy-two male Kunming mice were assigned randomly to different groups （n = 8 or n = 10）. MK-801 at 0. 25 mg/kg or 0. 5 mg/kg was used to induce hyperlocomotion or deficient PPI. Effects of haloperidol （0. 03, 0. 1 and 0. 3 mg/kg） on explorative behavior, spontaneous locomotion, MK-801-induced hyperactivity and were examined. Effects of halopefidol （0. 1,0. 3,1 mg/ kg） on intact and MK-801-disrupted PPI were examined. Results Haloperidol （0. 1 and 0. 3 mg/kg） significantly inhibited the explorative behavior and spontaneous locomotion （ P 〈 0. 05 ）. Haloperidol at 0. 03 mg/kg had no effect on exploration and spontaneous activity （ P 〉 0. 05 ）. Haloperidol （0. 1 - 0. 3 mg/kg） dose-dependently antagonized MK-801-induced hyperlocomotion （F = 27.23, P 〈 0. 01 ） , resulting in 22% and 65% reduction in total distance when administered at 0. 1 and 0. 3 mg/kg, respectively （P 〈 0. 01 ）. Haloperidol （0. 1 - 1mg/kg） dose-dependently enhanced baseline PPI （ F = 9.06, P 〈 0. 001 ） , resulting in 44% , 60% and 61% increase when administered at 0. 1,0. 3 and 1 mg/kg （ P 〈 0. 05 ） , respectively. Only the highest dose of Haloperidol （1 mg/kg） diminished MK-801-induced disruption of PPI （P 〈 0. 05 ）. Conclusions Haloperidol non-specifically inhibits the MK-801-induced hyperlocomotion and disruption of PPI.