2021 Fiscal Year Final Research Report
Identification of drug-sensitive ON cells to elucidate the underlying mechanism of CNS-acting drugs
| Project/Area Number |
19K16381
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 活性化細胞標識法 / 中枢神経作用薬 / cFos |
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| Outline of Final Research Achievements |
To elucidate the underlying mechanism of CNS-acting drugs, we attempted to perform a characteristic and functional analysis of drug-sensitive ON cells. In this study, we first generated genetically modified mice, which could especially express transgenes in cFos+ activated neurons under the administration of CNS-acting drugs according to the targeted recombination in active population (TRAP) method. Using these mice, we found the activation of neuronal cell subtypes related to brain reward systems by the administration of μ-opioid receptor agonist. Furthermore, we demonstrated that optogenetic reactivation of μ-opioid receptor agonist-responsive neurons in the ventral tegmental area could transiently modulate the pain threshold under a chronic pain-like state. These findings suggest that the characteristic and functional analysis of drug-sensitive ON cells using TRAP methods may help clarify the underlying pharmacological mechanism of CNS-acting drugs.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
中枢神経作用薬の primary site となる標的分子は明解となっているものの、実際に各薬物がどのような時間軸・空間軸で標的とする脳領域・細胞に到達し、作用発現を示すのかという分子・細胞メカニズムは不明である。本研究の成果より、遺伝子工学的手法を活用した活性化細胞標識法の応用により、中枢神経作用薬の脳領域・細胞への到達における時間軸や空間軸の違いや作用する標的細胞の違いに関して個別の薬物ごとにプロファイルを比較することが可能となった。このような研究アプローチは、各種中枢神経作用薬の分子細胞薬理学的な作用機構を理解するために重要性が高いと考えられる。
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