2016 Fiscal Year Final Research Report
Elucidation of novel drug dependent control mechanism focused on cytokine-chemokine network
| 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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| Keywords | methamphetamine / chemokine / place preference / dopamine receptor / prefrontal cortex / ventral tegmental area |
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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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| Free Research Field |
薬理学、薬物依存、疼痛学
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