title: Serotonin 1A receptor inhibits the status epilepticus induced by lithium-pilocarpine in rats.
abstract: 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 promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Yifang
authors.initials: Y
authors.lastname: Kuang
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yao
authors.initials: Y
authors.lastname: Ding
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Meiping
authors.initials: M
authors.lastname: Ding
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018021:Lithium Chloride / Q000633:toxicity*; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity*; D010862:Pilocarpine / Q000633:toxicity*; D010879:Piperazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013226:Status Epilepticus / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018721:Muscarinic Agonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D010862:Pilocarpine; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018021:Lithium Chloride