2014 Fiscal Year Final Research Report
The development of gene therapy with neuroimmune protein against drug addiction
Project/Area Number |
25860392
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Applied pharmacology
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
MURAKAMI Gen 浜松医科大学, 医学部, 特任研究員 (70613727)
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Keywords | 主要組織適合遺伝子複合体 / 薬物依存 / コカイン / 自己投与 / ドーパミン / 腹側被蓋野 |
Outline of Final Research Achievements |
MHC class I (MHCI), an important immune protein, contributes to eliminate synaptic connections in various brain regions, and its deficiency results in brain dysfunctions. However, the contribution of MHCI to addictive behaviors has not been considered. Here we found that repeated cocaine intakes persistently reduce MHCI expression particularly in dopamine neurons that is important for brain reward functions. This reduction leads to enduring potentiation of synaptic inputs to these neurons, resulting in robust cocaine-seeking behavior that is an animal model of relapse to cocaine. By contrast, cocaine-seeking behavior was suppressed by restoring the cocaine-induced reduction of MHCI in dopamine neurons. These results suggest that MHCI regulates synaptic transmission in dopamine neurons and its reduction underlies animal model of relapse to cocaine.
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Free Research Field |
医歯薬学
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