Effects of GABAB receptor antagonism on the development of Pentylenetetrazol-induced kindling in mice
Effects of GABAB receptor antagonism on the development of Pentylenetetrazol-induced kindling in mice
复制标题
DOI：
10.1016/s0006-8993(98)00864-6
复制
发表时间：
1998-11
期刊：
影响因子：
2.9
通讯作者：
D. Getova;W. Froestl;N. Bowery
中科院分区：
文献类型：
--
作者：
D. Getova;W. Froestl;N. Bowery
戊四唑（PTZ）长期给予啮齿动物诱导点火，这被认为是通过与gaba门控氯离子载体的特异性相互作用介导的慢性癫痫模型。PTZ点燃也损害了梭形盒学习，表明可能有记忆存储的调制[a]。贝克，G.格莱克施，H.马蒂斯。地西泮对戊四氮点燃后学习过程受损的影响。Naunyn-Schmiedeberg的拱门。药理学杂志，2004(3):429-496。GABABreceptor对抗以来显示改善认知能力的影响在啮齿动物和灵长类动物中,我们介绍了3拮抗剂:本金保证产品36742 (3-amino-propyl-n-butyl-phosphinic酸),本金保证产品56433 ([3 - {1 - (S) - [3 - (cyclohexylmethyl) hydroxyphosphinyl] {2 - (S)羟丙基)氨基)乙基)苯甲酸)和本金保证产品61334 ([3 - {[3 ((diethoxymethyl) hydroxyphosphinyl)丙基)氨基)甲基)苯甲酸酸)的感应PTZ火种在老鼠身上每隔48 h为8周。随后，小鼠在主动回避范式中进行了测试。实验结束时，对这些动物的脑切片进行gababr受体放射自显影。对照组小鼠的癫痫发作强度逐渐增加，达到8周的平均评分，与阵挛发作相对应。gababab拮抗剂在前4周抑制点燃，之后将癫痫发作强度恢复到对照动物的水平。点燃程度与回避得分成正比。PTZ点燃小鼠脑切片中gababr受体结合密度显著高于对照组。除小脑外，gababab拮抗剂预处理并未改变这一现象。
Pentylenetetrazol (PTZ) administered chronically in rodents induces kindling which is considered to be a model of chronic epilepsy mediated through a specific interaction with the GABA-gated chloride ionophore. PTZ kindling also impairs shuttle-box learning indicating a possible modulation of memory storage [A. Becker, G. Grecksch, H. Mathies. The influence of diazepam on learning processes impaired by pentylenetetrazol kindling. Naunyn-Schmiedeberg's Arch. Pharmacol. 349 (1994) 429-496]. Since GABABreceptor antagonism has been shown to improve cognitive performance in rodents and primates we have examined the effects of 3 antagonists: CGP 36742 (3-amino-propyl-n-butyl-phosphinic acid), CGP 56433 ([3-{1-(S)-[{3-(cyclohexylmethyl) hydroxyphosphinyl]-2-(S)-hydroxypropyl]-amino]ethyl]benzoic acid) and CGP 61334 ([3-{[3[(diethoxymethyl)hydroxyphosphinyl]-propyl]-amino}methyl]-benzoic acid) on the induction of PTZ kindling in mice at 48 h intervals for 8 weeks. Subsequently the mice were tested in an active avoidance paradigm. At the end of the experiment GABABreceptor autoradiography was performed on brain sections from these animals. Seizure intensity increased progressively in control mice reaching by 8 weeks a mean score which corresponded to clonic seizures. The GABABantagonists suppressed kindling during the first 4 weeks and after that restored the seizure intensity to the level of control animals. The level of kindling was proportional to the avoidance score. The density of GABABreceptor binding in brain sections from PTZ kindled mice was significantly greater than in controls. This was not altered by pretreatment with the GABABantagonists except in the cerebellum.