1996 Fiscal Year Final Research Report Summary
STUDY OF LONG TERM POTENTIATION (LTP) INDUCED IN VARIOUS BRAIN REGION AND ESTABLISHMENT OF NEW EVALUATION SYSTEM FOR NOOTROPIC DRUGS
| Project/Area Number |
07457542
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYUSYU UNIVERSITY |
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Principal Investigator |
WATANABE Shigenori KYUSHU UNIV.PHARMACEUTICAL SCI.PROFESSOR, 薬学部, 教授 (50037595)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Masuo KYUSHU UNIV.PHARMACEUTICAL SCI.ASSISTANT PROFESSOR, 薬学部, 助手 (60211801)
SHIMAZOE Takao KYUSHU UNIV.PHARMACEUTICAL SCI.ASSISTANT PROFESSOR, 薬学部, 助手 (00216053)
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| Project Period (FY) |
1995 – 1996
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| Keywords | long term potentiation (LTP) / nootropic drugs / hippocampus / suprachiasmatic nucleus (SCN) / striatum / ischemia / plasticity |
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| Research Abstract |
We studied long term potentiation (LTP) and neuronal plasticity in various brain regions, and clarified following points.
(1) LTP is induced in rat suprachiasmatic nucleus (SCN), and the induction is time-dependent. Methylcobalamin helps the induction of LTP in rat SCN.
(2) According to aging, the plasiticity reduces in rat SCN.
(3) It is well known that long term depression is induced in the striatum. However, ethanol abstinence induces LTP in rat striatum. NMDA receptors and dopaminergic receptors are involved in the induction of LTP in rat striatum.
(4) NO synthase inhibitors protects against hypoxia/hypoglycemia-induced decrease in CA1 presynaptic spikes in rat hippocampal slices. Ethanol abstinence potentiates hypoxia/hypoglycemic decrease in 2-deoxy-glucose uptake, but Ca channel blockers and glutathione protects the decrease. Moreover, Ca channel and sigma-receptors are involved in the hypoxia/hypoglycemica-induced impairment in rat hippocampus.
(5) NMDA receptors on dopaminergic nerve terminals in the striatum produces the long-term changes in efficacy of the response to KCL or glutamatergic agents. Metabotropic glutamate receptors may be involved in the expression of metamphetamine (MAP) -induced sensitization. Then, NO production plays a role in the expression of MAP-induced behavioral sensitization and enhancement of dopamine release.
(6) Concurrent blockade of hippocampal metabotropic glutamate and NMDA receptors disrupts working memory in the rat. b-adrenergic dysfunction exacerbates impairment of working memory induced by hippocampal NMDA receptor blockade in rats.
As described above, we first found that the LTP is induced in the SCN and the striatum. These results suggest that the neurons have the plasticity in various brain regions.
Because the precise mechanism is not well-known in dementia, various evaluation system is necessary to produce new effective nootropic drugs. Therefore, our study should be helpful for the evaluation of new nootropic drugs.
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