1996 Fiscal Year Final Research Report Summary
Development of animal models for Parkinson's desease and new drugs for this desease by the study of synaptic plasticity
| Project/Area Number |
07672366
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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 |
Biological pharmacy
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| Research Institution | Waseda University |
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Principal Investigator |
SHIBATA Shigenobu Waseda university, School of Human Sci., Dept.Pharmacol.Professor, 人間科学部, 教授 (10162629)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Parkinson / dopamine / circadian rhythm / long-term potentiation / plasticity / reserpine / suprachiasmatic nucleus / NMDA |
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| Research Abstract |
I tried to develop the model animals for Parkinson's desease by the study of synaptic plasticity. Long-term enhancemnet of dopamine release was obtained by high frequency tetanic stimulation via a N-methyl-D-aspartate (NMDA) receptor-mediated pathyway in rat striatal slices. Haloperidol which produces a catalepsy in the rat apparently reduced the NMDA- and tetanic stimulation-induced dopamine release from the striatum. In addition, NMDA-induced dopamine release was low in the aged animals. These results suggest that tetanic stimulation or NMDA receptor activation caused a synaptic plasticity in the striatum. Therefore, deficit of dopamine release in the striatum by tetanic or NMDA activation may become one of the animal models of Parkinson's desease. Impairment of locomotor activity induced by 6-OHDPAT or reserpine is widely used to evaluate the anti-Parkinson's drugs. In the present experiment, day/night differences of activity rhythm was observed in the reserpine-injected rats. In the next experiment, therefore I examined the effect of bromocriptine and taripexole on reserpine-induced impairment of wheel-running rhythm in the hamster. However, these chemicals did not attenuate the impairment. The present results suggest that dopamine release induced by tetanic stimulation or NMDA receptor activation may be related to the skillfulness of the motor function, and that a deficit of locomotor rhythm in reserpine-injected animals may not be useful to evaluate the anti-Pakinson's drug.
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[Publications] T.Moriya, Yamanouchi, S., Fukushima, T., Shimazoe, T., Shibata, S., Watanabe, S.: "Involvement of 5-HT1A receptor mechanisms in the inhibitory effects of methamphetamine on photic responses in the rodent suprachiasmatic nucleus" Brain Research. 740. 261-267 (1996)
Description
「研究成果報告書概要(欧文)」より
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