| Project/Area Number |
26860357
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Saika Fumihiro 和歌山県立医科大学, 医学部, 助教 (10644099)
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| Research Collaborator |
Wakida Naoki
Imai Kazuki
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | methamphetamine / chemokine / place preference / dopamine receptor / prefrontal cortex / ventral tegmental area / 薬理学 / 薬物依存 / ケモカイン / ドパミン受容体 / 前頭前皮質 / メタンフェタミン / 依存 / 脳・神経 / 神経炎症 / ドパミン / 腹側被蓋野 |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the molecular mechanism of drug dependence based on neuroinflammation in the brain reward system. We found that inflammatory chemokines (CCL7 and CCL2) were markedly upregulated in the prefrontal cortex after methamphetamine administration. Using pharmacological behavioral experiments, methamphetamine-induced addiction was attenuated by the antagonists of CCR2, a receptor that binds both CCL7 and CCL2. Furthermore, by histochemical analysis, chemokine receptor antagonist suppressed the activation of dopamine neurons by methamphetamine in the ventral tegmental area (the basis of the reward circuit). In conclusion, we demonstrate that the enhancement of brain reward system via chemokine signaling plays a crucial role in drug dependence on methamphetamine, and novel treatments targeting this machinery may be effective for drug addiction.
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