|Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Epileptic patients sometimes fall in the schizophrenia-like psychosis in their course of illness. These psychotic illness are called "epileptic psychosis". It has been suggested that epileptic psychosis may be caused by the damage of the temporal lobe or the limbic system. Epileptic psychosis is usually difficult to treat and the antipsychotic drug is not so effective. It is important to discover the mechanism of the epileptic psychosis and to establish the method of treatment.
Dizocilpine is a type of non-competitive NMDA receptor antagonist. It is known that dizocilpine causes schizophrenia-like psychotic symptoms and epileptic seizures in human and animal. Psychotic symptoms and epileptic seizures are caused by the neuronal damage which is probably concerned to the mechanisms of epileptic psychosis. So, we examined whether extracelullar dopamine, 5-HT and glutamate levels changed correspondind to the dizocilpine dose which cause the seizure and schizophrenia-like psychotic symptoms.
hronic experiments were carried out in 30 adult male rabbits. Procedures of animal care and use were in accordance with approved protocols of the Animal Research Committee of Kanazawa Medical University. Baseline recordings of the perforant path-dentate response elicited by single stimulations, which consisted of population spike (PS) and field EPSP, were carried out for 60 min. Next, vehicle solution, dizocilpine 0.5 mg/kg and 1.5 mg/kg were intraperitoneally administered; five rabbits were used for each dose. Then, recordings of the perforant path-dentate responses by single stimulations of the same stimulus strength as used for the baseline recording were carried out again for 60 min. Then, titanic stimulations were delivered to the perforant path to induce long-term potentiation (LTP) in the dentate gyrus, and subsequently stimulations of the same strength were given again for 60 min. dopamine and 5-HT concentrations were measured using the microdialysis technique. Dialysis samples were collected from the microprobe inserted into the dentate gyrus every 5 min. In the same methods, glutamate concentrations were measured in every five rabbits, as above mentioned.
Eventually, dizocilpine did not change the perforant path-dentate responses at any doses, with PS and EPSP. Dizocilpine prevented LTP induction in doses of the 0.5 mg/kg and 1.5 mg/kg. However, at any doses, dopamine, 5-HT and glutamate levels were not changed at all.
It has been reported that dizocilpine increase dopamine and acetylcholine levels in prefrontal cortex in rat. Present results show that dizocilpine produces no changes in dopamine, 5-HT and glutamate levels in the hippocampus. Less