Project/Area Number |
12670586
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Hirosaki University |
Principal Investigator |
MATSUNAGA Muneo Hirosaki University School of Medicine, Professor, 医学部, 教授 (80003599)
|
Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Masahiko Hirosaki University School of Medicine, Assistant, 医学部, 助手 (40311542)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | 6-OH model rat / dyskinesia / motor sensitization / GABAergic neuron / 5-HT agonist / glutamic acid decarboxylase / pallidotomy / subthalamic nucleus stimulation / セロトニンニューロン / ドパミン代謝 / NMDA型グルタミン酸受容体 / In vivo microdialysis / In situ hybridization / レボドパ / in vivo microdialysis / in situ hybridization |
Research Abstract |
To determine the effects of a 5-hydroxytryptamine (5-HT)_<1A> agonist, 8-OH-DPAT, on behavioral sensitization induced by intermittent administration of levodopa in 6-hydroxydopamine (6-OHDA) rats, we elucidated rotational behavior and messenger RNAs coding prodynorphin (DYN) and glutamic acid decarboxylase (GAD) in the dopamine-denervated striatum of 6-OHDA-lesioned rats which repeatedly received either saline or levodopa or 8-OH-DPAT plus levodopa twice a day for two weeks. Rotational behavior was markedly increased in 6-OHDA-lesioned rats treated with intermittent levodopa. However, coadministration of 8-OH-DPAT with levodopa attenuated the increase of circulation behavior. Expression of GAD and DYN mRNAs was significantly increased in the dopamine denervated striatum of 6-OHDA-lesioned rats after intermittent levodopa treatment, whereas additional 8-OH-DPAT administration significantly suppressed increases of their expression. These results suggest that 5-HT_<1A> receptor agonists can alleviate levodopa-induced motor complications in Parkinson's disease.
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