Increase in drug-induced seizure susceptibility of transgenic mice overexpressing GABA transporter-1

	Increase in drug-induced seizure susceptibility of transgenic mice overexpressing GABA transporter-1
	Zhao, WJ; Ma, YH; Fei, J; Mei, ZT; Guo, LH
刊名	ACTA PHARMACOLOGICA SINICA
	2003
卷号	24 期号:10 页码:991-995
关键词	neutrotransmitter transporter carrier proteins seizures GABA pentylenetetrazol picrotoxin kainic acid ethyl nipecotate transgenic mice
通讯作者	Guo, LH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,lhguo@sunm.shcnc.ac.cn
英文摘要	AIM: The changes of seizure susceptibility of transgenic mice overexpressing GABA transporter-1 (GAT-1) were studied to clarify the possible role of GABAergic transmission in epileptogenesis. METHODS: Seizures were induced by intraperitoneal administration of pentylenetetrazol (PTZ), picrotoxin (PIC), or kainic acid (KA) respectively. The anticonvulsant effect of ethyl nipecotate was tested by its intraperitoneal injection 15 min before the administration of the epileptogenic agents. RESULTS: The percentages of occurrence of clonic seizures induced by PTZ 45 mg/kg, PIC 2.5 mg/kg, or KA 20 mg/kg in GAT-1 transgenic mice were 88.9 %, 100 %, and 83.3 % respectively, whereas those in control C57BL/6J mice were 42.9 %, 57.1 %, and 33.3 %. The percentages of occurrence of tonic seizures induced by PTZ 45 mg/kg, PIC 2.5 mg/kg, or KA 20 mg/kg in transgenic mice were 88.9 %, 100 %, and 83.3 % respectively, and whereas those in control mice were 28.6 %, 42.9 %, and 16.7 %. The latencies of both clonic and tonic seizures onset in transgenic mice were markedly shortened compared with those in control animals. The results indicated that GAT-1 transgenic mice showed increased susceptibility to seizures induced by the anti-GABAergic convulsive drugs (PTZ, PIC), as well as glutamic receptor agonist (KA). Ethyl nipecotate, inhibitor of GAT-1, inhibited PTZ-induced seizures in both GAT-I transgenic and C57BL/6J mice. The incidence of seizures was decreased after the application of ethyl nipecotate, and the latencies to the onset of clonic or tonic seizures were also prolonged. CONCLUSION: The increase in seizure susceptibility of transgenic mice over-expressing GAT-1 is an evidence for involvement of GABAergic transmission in epileptogenesis, and this transgenic mouse might be a useful animal model for study on the role of GABAergic transmission in epileptogenesis.
学科主题	Chemistry; Pharmacology & Pharmacy
类目[WOS]	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
关键词[WOS]	SUBTYPE-I LEADS ; UPTAKE INHIBITOR ; AMINO-ACIDS ; KAINIC ACID ; EPILEPSY ; GLUTAMATE ; TIAGABINE ; BRAIN ; RAT ; ANTICONVULSANT
收录类别	SCI
语种	英语
WOS记录号	WOS:000185749400006
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2358]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhao, WJ,Ma, YH,Fei, J,et al. Increase in drug-induced seizure susceptibility of transgenic mice overexpressing GABA transporter-1[J]. ACTA PHARMACOLOGICA SINICA,2003,24(10):991-995.
APA	Zhao, WJ,Ma, YH,Fei, J,Mei, ZT,&Guo, LH.(2003).Increase in drug-induced seizure susceptibility of transgenic mice overexpressing GABA transporter-1.ACTA PHARMACOLOGICA SINICA,24(10),991-995.
MLA	Zhao, WJ,et al."Increase in drug-induced seizure susceptibility of transgenic mice overexpressing GABA transporter-1".ACTA PHARMACOLOGICA SINICA 24.10(2003):991-995.