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Preclinical studies on the therapy of epilepsy and epileptic psychosis.

癫痫和癫痫精神病治疗的临床前研究。

基本信息

批准号：
08671125
负责人：
MINABE Yoshio
金额：
$ 1.47万
依托单位：
National Institute of Neuroscience
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671125/
关键词：
Epilepsy Excitatory Amino Acids Heat Shock Protain Hippocampus Dopamine Serotonin Neuropeptides Sigma receptor

项目摘要

1. Using an animal model of partial hippocampal seizure, we investigated the effects of verious drogs on seizure parameters. AMPA receptor antagonists showed a similar profile with carbamazepine by increasing the seizure threshold. NMDA receptor antagonists also increased the seizure threshold and GABA agonists decreased the duration of seizure. K^+-channel openers showed a similar profile with Ca^<++>-channel blockers by decreasing the seizure duration. Antisense c-fos ODN also decreased the seizure duration.2. Heat shock protain (HSP) was introduced by only 10-min duration seizure after the application of adenosin I receptor antagonist plus electrical stimulation into the hippocampus. The epileptic status by kainic acid i.p.introduced HSP,BDNF and COX-2 mRNA expression.3. The expression of HSP protain, but not of necrotic change in the rat cortex caused by NMDA receptor antagonists was blocked by AMPA receptor antagonists, muscarinic receptor antagonists and cAMP phosphodiesterase inhibitors.4. Using the in vivo extracellular single-unit recording technipue, we examined the effect of various drugs on the spontaneously active dopamine cells of A9, A10 area. Serotonin Ia agonists or IIa, IIc antagonists showed a similar profile with antipsychotics. Sigma receptor agonists showed a similar profile with antidepressants. During the withdrawal period after cocaine or MDMA chronic injection, dopamine cell function of A10 area was suppressed.

1. 采用海马部分性癫痫动物模型，研究了不同药物对癫痫发作参数的影响。AMPA受体拮抗剂与卡马西平表现出相似的特征，即增加癫痫发作阈值。NMDA受体拮抗剂也增加了癫痫发作阈值，而GABA激动剂减少了癫痫发作的持续时间。K^+通道打开剂与Ca^<++>通道阻滞剂表现出相似的特征，通过减少癫痫发作持续时间。反义c-fos ODN可明显缩短癫痫发作时间。热休克蛋白（HSP）是在应用腺苷I受体拮抗剂加电刺激海马后仅持续10分钟的癫痫发作中引入的。kainic acid ipp诱导大鼠HSP、BDNF和COX-2 mRNA表达。AMPA受体拮抗剂、毒蕈碱受体拮抗剂和cAMP磷酸二酯酶抑制剂可阻断NMDA受体拮抗剂引起的大鼠皮质坏死变化，而非HSP蛋白的表达。采用体内细胞外单单位记录技术，观察了不同药物对A9、A10区自发活性多巴胺细胞的影响。血清素IIa激动剂或IIa、IIc拮抗剂与抗精神病药物表现出相似的特征。西格玛受体激动剂与抗抑郁药表现出相似的特征。慢性注射可卡因或MDMA停药期间，A10区多巴胺细胞功能受到抑制。