Preclinical studies on the therapy of epilepsy and epileptic psychosis.

1.采用部分性海马区癫痫动物模型，观察不同剂量Drogs对癫痫发作参数的影响。AMPA受体拮抗剂通过提高癫痫阈值，表现出与卡马西平相似的特征。NMDA受体拮抗剂也提高了惊厥阈值，GABA激动剂则缩短了惊厥持续时间。K^+通道开放剂与钙通道阻滞剂在缩短癫痫发作持续时间方面表现出相似的特征。结论：1.反义c-fos ODN能明显缩短癫痫发作时间。应用腺苷I受体拮抗剂加电刺激大鼠海马区，仅持续惊厥10min，即可产生热休克蛋白(HSP)。海人酸致痫状态诱导HSP、BDNF和COX-2mRNA的表达。AMPA受体拮抗剂、M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大脑皮质HSP蛋白的表达，但不能抑制其坏死性改变。采用细胞外单单位记录技术，观察了不同药物对A9、A10区自发性兴奋的多巴胺细胞的影响。5-羟色胺Ia激动剂或IIa、IIc拮抗剂表现出与抗精神病药物相似的特征。Sigma受体激动剂表现出与抗抑郁药相似的特征。在可卡因或MDMA慢性注射后的戒断期间，A10区的多巴胺细胞功能受到抑制。

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.