Preclinical studies on the therapy of epilepsy and epileptic psychosis.

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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.