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。使用部分海马癫痫发作的动物模型，我们研究了ver虫对癫痫发作参数的影响。 AMPA受体拮抗剂通过增加癫痫发作阈值而显示出与卡马西平相似的特征。 NMDA受体拮抗剂还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^+ - 通道开启器通过减少癫痫发作持续时间，显示出具有CA^<++> - 通道阻滞剂的相似轮廓。反义C-FOS ODN也降低了癫痫发作持续时间2。热休克蛋白（HSP）仅在将腺苷I受体拮抗剂加上电刺激加入海马后仅10分钟的持续时间癫痫发作引入。 Kainic Acid I.P.介绍的HSP，BDNF和COX-2 mRNA表达的癫痫状态3。 AMPA受体拮抗剂，毒蕈碱受体拮抗剂和CAMP磷酸二酯酶抑制剂阻止了HSP蛋白质的表达，但没有由NMDA受体拮抗剂引起的大鼠皮质变化。4。使用体内细胞外单单元记录技术，我们检查了各种药物对A9，A10区域自发活性多巴胺细胞的影响。 5-羟色胺IA激动剂或IIA，IIC拮抗剂在抗精神病药上表现出相似的特征。 Sigma受体激动剂与抗抑郁药显示出相似的特征。在可卡因或MDMA慢性注射后的戒断期间，A10区域的多巴胺细胞功能被抑制。