目的 观察5-羟色胺6受体拮抗剂SB-271046对匹罗卡品致痫大鼠空间学习记忆的作用效应.方法 成年雄性SD大鼠分为两组:空白对照组(Vehicle组,n=10),氯化锂-匹罗卡品组(Lithium chloride-Pilocarpine,LiCl-PILO组,n=40).首先根据注射LiCl-PILO后是否出现癫痫持续状态(Status Epilepticus,SE),出现SE者纳入实验,未出现SE和死亡者则剔除;然后再随机分为3组:模型组即侧脑室注射羟丙基-β-环糊精(Hydroxypropyl-β-cyclodextrine,HP-β-CD),4μl;药物组按不同剂量分为2组,即侧脑室注射N-[4-Methoxy-3-(4-methyl-1-piperazinyl)-phenyl]-5-chloro-3-methylbenzo-thiophene-2-yl-sulphonamide monohydrochloride(SB-271047)剂量为10μg,4μl和侧脑室注射SB-271046剂量为20μg,4μl.结果 在Y迷宫自主交替行为实验中,模型组自主交替率显著下降(P<0.01),药物组显著提高尤其是20μg剂量组(P<0.05).在Y迷宫新奇事物探索实验中,模型组的新臂时间比显著下降(P<0.01),药物组有提高趋势(P>0.05).在Morris水迷宫定位航行实验中,模型组平均潜伏期延长显著延长(P<0.01),药物组明显缩短尤其是20μg剂量组(P<0.05).在Morris水迷宫空间探索实验中,模型组平均潜伏期延长,穿越平台次数减少,原平台象限停留时间缩短(P<0.05),药物组有改善趋势(P>0.05).结论 SB-271046可以改善癫痫大鼠的空间学习记忆,主要作用于记忆获得巩固阶段,20μg剂量作用明显.%Objective Our primary objective is to investigate the effects of 5-HT6 receptor antagonist SB-271046 on spatial learning-memory in pilocarpine-induced epileptic rats. Methods 50 male adult Sprague-Dawley rats were divided into 2 groups,vehicle control group (n=10) and pilocarpine(PILO) treated group (n=50). Status epilepticus (SE) of rats was induced by intraperitoneal ( i. p. ) injection of LiCl-pilocarpine. According to Racine classify,seizures up to IV and last more than 30mins are supposed to be SE. Rats with successful SE were then divided into 3groups:mode control group (HP-CD,lateral ventricle (LV)injection with HP-β-CD,4 μl),10 μg-SB271046 group(10 μg-SB,LV injection with SB-271046,4μl),20μg-SB271046 group(20μg-SB,LV injection with SB-271046,4μl). Unsuccessful SE rats and died rats were both excluded from our experiment. Spatial learning-memory was evaluated to all groups by Y-maze and Morris water maze after 6 weeks. Results In Y-maze spontaneous alternation behavior test(SAB),We found significant decreasing of alternation rate in HP-CD group(P<0. 01). Besides,we saw reversion of alternation rate in the rats in SB-271046 injected groups,especially 20 μg-SB271046 group(P<0. 05). In Y-maze novel object discrimination 4h ITI test(NOD),new arm percentage of HP-CD also decreased significantly(P<0. 01),but SB-271046 didn't reverse this defect. In Morris water maze acquisition stage,the latency of different groups were gradually shorten from day 1 to day 5;meanwhile,the mean la-tency of the rats in HP-CD was prolonged significantly(P<0. 01),the most obvious improvement also was found in 20 μg-SB271046 group(P<0. 05). In retention stage,the results of 3 items: means latency,numbers of crossing target and per-centage of performance time in target zone indicated the memory of rats in HP-CD group were damaged,SB-271046 didn' t reverse the defects. Conclusion 5-HT6 receptor antagonist SB-271046 can reverse epileptic rats' spatial learning-memory defect,especially in acquisition stage,and maybe have dose-effect relationship.
展开▼
