西酞普兰对戊四氮点燃癫痫大鼠行为学及海马5-HT能递质系统影响的在体微透析研究

Effect of citalopram on pentylenetetrazol-induced kindling rat's behavior and hippocampal 5-HTergic systems in vivo microdialysis

为研究5-羟色胺(5-HT)能神经递质在癫痫形成过程中的变化及西酞普兰(CTP)对其的影响,本研究用CTP(1mg/kg.d灌胃)预干预1周后,对戊四氮(PTZ,30mg/kg.d,腹腔注射)点燃癫痫过程中的行为学及在不同时间点对大鼠海马进行微透析取样,经高效液相电化学检测技术在活体观察了30只自由活动大鼠5-HT及其代谢产物5-羟吲哚乙酸(5-HIAA)水平和5-HT转化率(5-HIAA/5-HT)的动态变化。结果显示:PTZ注射后在CTP组发作潜伏期延长,发作程度轻和点燃时间延长,发作死亡率降低。点燃早期,CTP组大鼠的海马5-HT水平升高,5-HT转化率降低,与对照组和PTZ组比较,有显著性差异(P<0.05);点燃晚期CTP组和PTZ组与对照组比较5-HT水平和5-HT转化率均显著降低(P<0.05)。本研究结果提示PTZ点燃过程中,早期CTP升高脑内5-HT水平,可能直接抑制了引起爆发放电的动作电位,而抑制发作;晚期脑内5-HT神经元丢失和受体减少,功能减退,而导致CTP的作用减退。

To investigate the change and the effect of eitalopram on the the pentylenetetrazol-induced kindling rat＇s serotonin-ergic （5-HTergic） systems, we administrated citalopram [CTP,1 mg/kg· d）] intragastric one week before pentylenetetrazol [PTZ,30 mg/（kg·d）] intraperitoneal injection, and observed behavior everyday. At 14 d and 28 d, microdialysis was run in the hippoeampus of rats, and dialysate was collected. In the dialysate, concentrations of extraeellular 5-HT, and its metabolite 5-hydroxyindolacetic acid （5-HIAA） were assessed by HPLC. The results showed the concentrations of 5-HT in the hippocampus were significantly increased at 14 d and 5-HT turnover （5-HIAA/5-HT） decreased during PTZ-induced seizures intervention by CTP compared with the control （P〈0.05）. But in the only PTZ-induced group, the concentrations of 5-HT were significantly decreased compared with the control （P〈0.05）. In the advanced stage of kindling （at 28 d） , the CTP group as well as the PTZ only group were significantly decreased in concentrations of 5-HT compared with the control. These results suggest that the increase of 5-HT concentrations by CTP in the hippoeampus are probably related to inhibit the abnormal discharge induced by PTZ, and finally inhibiting seizures in rats; but in advanced stage, because of depletion of serotonin and down-regulation of 5-HT receptors, effect of CTP was gone down.