1999 Fiscal Year Final Research Report Summary
下行性の筋緊張制御における脊髄のセロトニン1Aおよび2受容体の役割
| Project/Area Number |
09672258
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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 | Science University of Tokyo |
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Principal Investigator |
ONO Hideki Science University of Tokyo, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00080200)
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| Project Period (FY) |
1997 – 1999
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| Keywords | serotonin receptor / muscle tone / spinal cord / serotonin release |
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| Research Abstract |
Descending serotonergic neurons originated from the Raphe nuclei innervate spinal motoneurons, and control muscle tone and locomotion. However, the subtypes of the serotonergic receptors and the detailed mechanisms of action are still unclear. In the present study, we studied the followings using the measurement of spinal reflex potentials and serotonin release from the spinal cord in adult rats.
1.8-OH-DPAT is widely used as an agonist for 5-HT1A receptor. In this study, we showed that the R- and S-isomers facilitate the spinal motor activity via different types of receptors. At the spinal cord level, the R-isomer depressed the monosynaptic reflex via receptors other than 5-HT1A.
2.We showed that cyclobenzaprine, and amitriptyline and cyproheptadine, analogs of cyclobenzaprine blocked the 5-HT2 receptors in the spinal cord, and consequently depressed the monosynaptic reflexes. Involvement of 5-HT2 receptors in motor stimulatory role of serotonergic systems was elucidated.
3.Serotonin released from the terminals of descending serotonergic neurons was measured using spinal subarachnoid space perfusion methods. Amitriptyline which blocks 5-HT2 receptors in the spinal cord did not increase serotonin. From this result, uptake inhibitory action of amitriptyline to serotonin was considered to be weaker than 5-HT2 receptor blocking action. Diazepam, which has muscle relaxant action, reduced the release of serotonin.
These results suggest that spinal motor systems are facilitated by descending serotonergic systems, especially via 5-HT2 receptors. On the other hand, it was suggested that 5-HT receptors other than 5-HT1A inhibited spinal motor systems.
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