| Project/Area Number |
15K08603
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北中 順惠 兵庫医科大学, 医学部, 講師 (30340954)
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| Research Collaborator |
AMATSU YUKIE
HASHIMOTO KOTAKU
HISATOMI ERINA
KANDORI TAKASHI
KITAO ERI
MIMURA MARI
MURAKAMI AYAKA
MURATANI KAZUKI
NAKAMURA MIYU
NAKANO TAE
OZAWA RENA
SATO MIHO
TAGAMI KENTA
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | 覚せい剤 / 中枢ヒスタミン神経系 / アグマチン / ヒスタミンH3受容体逆作動薬 / ヒスタミンNメチル基転移酵素 / 視床下部 / 過運動 / 高速液体クロマトグラフィー / JNJ-10181457 / 麻薬 / ピトリサント / 循環系作用 / 常同行動 / メマンチン |
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| Outline of Final Research Achievements |
We have previously reported that methamphetamine (METH)-induced abnormal behaviors such as hyperlocomotion and stereotypy in rodents are attenuated by treatment with histamine inactivating enzyme inhibitor HMT (histamine N-methyltransferase) which increases brain histamine levels. In this project, we have searched chemical compounds which effectively release histamine in brain and activate brain histaminergic neuronal system, and found that three compounds (agmatine, pitolisant, and JNJ-10181457) effectively released histamine in the hypothalamus, and that they attenuated METH-induced hyperlocomotion and stereotypy in mice. These compounds did not exhibit unexpected side effects so that they might be candidates of pharmacotherapy for METH addiction and abuse. A possible association of histaminergic activation with suppression of stereotypy is also found in this project using mice showing memantine-induced stereotyped behavior.
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