1998 Fiscal Year Final Research Report Summary
Research on the toxicity of free radicals as a factor for the methamphtamine psychosis
| Project/Area Number |
09670982
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
MATSUNAGA Tsutomu Hamamatsu University School of Medicine Department of Psychiatry and Neurology, Research Associate, 医学部附属病院, 助手 (10273179)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Norio Hamamatsu University School of Medicine Department of Psychiatry and Neurology,, 医学部, 教授 (00174376)
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| Project Period (FY) |
1997 – 1998
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| Keywords | methamphetamine psychosis / schizophrenia / methamphetamine / hydrogen peroxide / rat / in vivo / electrochemical detection / MK-801 |
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| Research Abstract |
We established a method for measuring a concentration of hydrogen peroxide in vivo in the free moving rat brain using a microelectrodes system. Utilizing this method) we demonstrated an increase in concentration of hydrogen peroxide in the rat striatum after acute methamphetamine (MAP) administration. Increase in concentration of hydrogen peroxide was not blunted after a continuous infusion of MAP for 7 days, which has been shown to be enough for resulting sever injury of dopamine nerve terminals in the striatum. These results suggest that even after a sever nerve injury caused by chronic MAP use, a reuse of MAP causes increase in hydrogen peroxide in the striatum that may further injure the nervous system.
A sensitization to MAP is supposed to be a model of recurrence of schizophrenia. Co-administration of MK-801, a non-competitive NMDA receptor antagonist, inhibits a sensitization to MAP.This suggests that signal transmission via NMDA receptors is closely involved in the neural substr
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ates of sensitization to MAP, as well as pathophysiology of schizophrenia. On the other hand, it is reported that co- administration of MK-801 does not prevent a nerve injury caused by acute administration of MAP.Cell toxicity of MAP is thought to be due to hydrogen peroxide generated in the process of dopamine degeneration. Therefore, we investigated whether or not co-administration of MK-801 influences hydrogen peroxide generation by MAP, and whether or not the administration of MK-8O1 alone causes an alteration of hydrogen peroxide concentration in the rat striatum.
In our results, co-administration of MK-801 did not influence the hydrogen peroxide concentration in the striatum after MAP injection. Acute administration of MK-801 alone also increased in the concentration of hydrogen peroxide in the rat striatum. These results suggest the reason why co-administration of MK-801 does not prevent nerve injury caused by MAP administration and MK-801, potential therapeutic agent for preventing a sensitization to MAP, may have cell toxicity. Less
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