Status epilepticus(SE) is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A(5-HT1A) receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride(LiCl; 3 meq/kg, i.p.) 22–24 h prior to pilocarpine(25 mg/kg, i.p.), and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously(s.c.) at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures(GS), while reducing the total EEG seizure time(P <0.01). The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c.(P <0.05). All these effects were inhibited by combined administration of WAY-100635(1.0 mg/kg, s.c.)(P <0.05), an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OHDPAT(0.01 and 0.1 mg/kg) did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration(P <0.05). These findings imply that the 5-HT1A receptor is a promisingtherapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.
Yi YangYi GuoYifang KuangShan WangYan JiangYao DingShuang WangMeiping Ding
