PHARMACOLOGICAL AND BIOCHEMICAL STUDIES OF AMYGDALA KINDLING
杏仁核点燃的药理学和生物化学研究
基本信息
- 批准号:3781441
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:acetylcholine alpha adrenergic receptor amygdala anticonvulsants benzodiazepine receptor carbamazepine corticotropin releasing factor electrostimulus gene induction /repression generalized seizures kindling laboratory rat neuropharmacology protooncogene thyrotropin releasing hormone valproate yohimbine
项目摘要
The objectives of this project are to understand and modulate the course
of development of amygdala-kindled seizures. The effects of carbamazep-
ine and other anticonvulsants on amygdala kindling have been examined in
relation to stage of kindled seizure development (as well as type of
kindling stimulus; see Z01 MH 02528-03 BP). Agents with specific biolog-
ical target systems have been used to attempt to modulate carbamazepine's
anticonvulsant effects on kindled seizures, in order to elucidate carbam-
azepine's mechanisms of action. Finally, studies addressing possible
mechanisms of amygdala kindling have been conducted with Drs. Mike Clark,
Jeff Rosen, Russel Margolis, De-Maw Chuang, Mark Smith and Trino Baptis-
ta. Significant findings to date include demonstration of the following.
1) carbamazepine is an effective anticonvulsant agent during the complet-
ed phase of amygdala kindling, but not during seizure development; 2)
valproic acid is an effective anticonvulsant agent against both seizure
development and completed seizures; 3) carbamazepine's anticonvulsant
effects can be reversed by agents that act at the peripheral-type benzod-
iazepine receptor (Ro5-4864) and the alpha-2-noradrenergic receptor
(yohimbine); 4) amygdala-kindled seizures, electroconvulsive shock
seizures, and after discharge activity in the amygdala (without general-
ized seizures) can induce CRH-mRNA in the hippocampus, in cells which do
not normally express CRH message; 5) kindled seizure development (seizure
stage 1-2 or after discharges only) is associated with increased acetyl-
choline levels in the amygdala contralateral to the electrode; a less
robust increase is observed in fully kindled animals (stage 5 seizures);
6) lesions of the olfactory bulb do not affect the development of amygda-
la-kindled seizures or anticonvulsant responsivity to carbamazepine,
valproate, or diazepam; 7) time off from seizures, in kindled rats,
produces anticonvulsant refractoriness upon subsequent testing; 8) a
decrease in seizure threshold (i.e., increased seizure susceptibility) is
associated with 5 days of time off from seizures; 9) the proto-oncogene
c-fos is induced in a regionally selective manner during kindling devel-
opment, which, in the early stages of kindling, is dependent upon the
length of the elicited afterdischarge duration; and 10) the mRNA for TRH
is increased with amygdala kindling, in roughly the same areas as the
c-fos expression.
本计画的目的是了解并调整课程
杏仁核引发癫痫的可能性 卡马西平的作用-
在杏仁核点燃的研究中,
与点燃癫痫发作发展阶段的关系(以及
点燃刺激;参见Z 01 MH 02528-03 BP)。 具有特定生物标志物的药剂-
已经使用了化学靶向系统来尝试调节卡马西平的
对点燃癫痫发作的抗惊厥作用,以阐明carbam-
Azepine的作用机制 最后,研究解决可能的
杏仁核点燃的机制已经由Mike Clark博士进行,
杰夫罗森,罗素马戈利斯,庄德茂,马克史密斯和特里诺巴普蒂斯-
ta.迄今为止的重要调查结果包括以下方面的证明。
1)卡马西平是一种有效的抗惊厥剂,
杏仁核点燃的艾德阶段,但不是在癫痫发作发展期间; 2)
丙戊酸是一种有效的抗惊厥剂,
发展和完成癫痫发作; 3)卡马西平的抗惊厥药
作用于外周型苯并三唑的试剂可以逆转这种效应,
氮杂卓受体(Ro 5 -4864)和α-2-去甲肾上腺素能受体
(育亨宾); 4)杏仁核点燃癫痫发作,电休克
癫痫发作和杏仁核放电后活动(无全身性-
癫痫发作)可以诱导海马CRH-mRNA,在细胞中,
不正常表达CRH信息; 5)点燃癫痫发作(癫痫发作
阶段1-2或仅在放电后)与乙酰基增加有关,
电极对侧杏仁核中的胆碱水平;
在完全点燃的动物中观察到显著增加(第5阶段癫痫发作);
6)嗅球的损伤不影响杏仁核的发育,
LA点燃癫痫发作或抗惊厥药对卡马西平的反应,
丙戊酸盐或地西泮; 7)癫痫发作的停止时间,在点燃大鼠中,
在随后的测试中产生抗惊厥药难治性; 8)a
癫痫发作阈值的降低(即,增加癫痫发作的敏感性),
与5天的时间从癫痫发作; 9)原癌基因
c-fos在点燃发育过程中以区域选择性的方式被诱导,
在点燃的早期阶段,它依赖于
诱发后放电持续时间的长度;和10)TRH的mRNA
杏仁核点燃时,
c-fos表达。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
S R WEISS其他文献
S R WEISS的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('S R WEISS', 18)}}的其他基金
PHARMACOLOGICAL AND BIOCHEMICAL STUDIES OF AMYGDALA KINDLING
杏仁核点燃的药理学和生物化学研究
- 批准号:
5203746 - 财政年份:
- 资助金额:
-- - 项目类别:
相似海外基金
MOLECULAR BASIS OF ALPHA ADRENERGIC RECEPTOR FUNCTION
α 肾上腺素能受体功能的分子基础
- 批准号:
6110455 - 财政年份:1999
- 资助金额:
-- - 项目类别:
MOLECULAR BASIS OF ALPHA ADRENERGIC RECEPTOR FUNCTION
α 肾上腺素能受体功能的分子基础
- 批准号:
6273039 - 财政年份:1998
- 资助金额:
-- - 项目类别:
MOLECULAR BASIS OF ALPHA ADRENERGIC RECEPTOR FUNCTION
α 肾上腺素能受体功能的分子基础
- 批准号:
6242449 - 财政年份:1997
- 资助金额:
-- - 项目类别:
Central and renal alpha-adrenergic receptor with the development of salt-induced hypertension in Dahl-Iwai salt-sensitive rats.
中枢和肾脏 α-肾上腺素能受体与 Dahl-Iwai 盐敏感大鼠中盐诱导高血压的发展。
- 批准号:
03670461 - 财政年份:1991
- 资助金额:
-- - 项目类别:
Grant-in-Aid for General Scientific Research (C)
IDENTIFICATION AND FUNCTION OF ALPHA-ADRENERGIC RECEPTOR
α-肾上腺素能受体的鉴定和功能
- 批准号:
3079007 - 财政年份:1983
- 资助金额:
-- - 项目类别: