2015 Fiscal Year Final Research Report
Role of PDEs in antipsychotic effects in hippocampal dentate gyrus.
| Project/Area Number |
26860951
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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 |
Psychiatric science
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | ホスホジエステラーゼ / 海馬歯状回 / ドーパミン / 抗うつ薬 |
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| Outline of Final Research Achievements |
Male DISC1-DN-Tg-PrP and their male littermate Wild-type mice were group-housed or isolated from 5 weeks of age. After the isolation stress, the PDE functions were alterd in the nucleus accumbens and in the striatum. In addition, the same result was suggested in the hippocampal dentate gyrus.
Furthermore, we observed that chronic treatment of C57BL/6 mice with fluoxetine induced the expression of D1 receptors in granule cells. The high expression of D1 receptors resulted in activation of cAMP/PKA signaling in the dentate gyrus. In behavioral studies, D1 receptor agonism enhanced antidepressant action of fluoxetine in mice subjected to chronic restraint stress. Thus, D1 receptors in granule cells, induced by chronic antidepressants, enhance antidepressant effects under stressed conditions. Dopamine D1 receptors may be a therapeutic target of depression.
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| Free Research Field |
中枢神経薬理
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