2012 Fiscal Year Final Research Report
Neuropharmacological study on drug development targeting forbrain metabotropic glutamate 2/3 receptors
| Project/Area Number |
23790599
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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 | Osaka University |
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Principal Investigator |
AGO Yukio 大阪大学, 大学院・薬学研究科, 助教 (50403027)
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| Project Period (FY) |
2011 – 2012
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| Keywords | うつ病 / 代謝型グルタミン酸2/3受容体 (mGlu2/3受容体) / 環境要因 / グルココルチコイド / グリア細胞 / 大脳皮質前頭前野 / 海馬 / ドパミン |
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| Research Abstract |
Only 30-50% of patients with depression enter remission after antidepressant treatment. Thus, discovering novel neuronal mechanisms of pathophysiology of depression as well as more effective treatments are necessary. In this study, metabotropic glutamate 2/3 receptor antagonists showed antidepressant-like effects in chronic glucocorticoid-treated mice, an animal model of conventional antidepressant-resistant depression. Chronic glucocorticoid treatment markedly increased prefrontal dopaminergic activity, and this enhanced activity was blocked by metabotropic glutamate 2/3 receptor antagonists, but not conventional antidepressants. The present findings suggest that the metabotropic glutamate 2/3 receptor is a promising target for the treatment of patients with treatment-resistant depression.
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[Journal Article] Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice2013
Author(s)
Yukio Ago, Koji Yano, Ryota Araki, Naoki Hiramatsu, Yuki Kita, Toshiyuki Kawasaki, Hirotaka Onoe, Shigeyuki Chaki, Atsuro Nakazato, Hitoshi Hashimoto, Akemichi Baba, Kazuhiro Takuma, Toshio Matsuda
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Journal Title
Neuropharmacology
Volume: vol. 65
Pages: 29-38
DOI
Peer Reviewed
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[Journal Article] The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses psychomotor abnormalities and recognition memory deficits in mice lacking the pituitary adenylate cyclase-activating polypeptide.2013
Author(s)
Yukio Ago, Naoki Hiramatsu, Toshihiro Ishihama, Keisuke Hazama, Atsuko Hayata-Takano, Yasuhiro Shibasaki, Norihito Shintani, Hitoshi Hashimoto, Toshiyuki Kawasaki, Hirotaka Onoe, Shigeyuki Chaki, Atsuro Nakazato, Akemichi Baba, Kazuhiro Takuma, Toshio Mat
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Journal Title
Behavioural Pharmacology
Volume: vol. 24
Pages: 74-77
DOI
Peer Reviewed
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[Journal Article] The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses isolation rearing-induced abnormal behaviors in mice2012
Author(s)
Yukio Ago, Ryota Araki, Koji Yano, Toshiyuki Kawasaki, Shigeyuki Chaki, Atsuro Nakazato, Hirotaka Onoe, Hitoshi Hashimoto, Akemichi Baba, Kazuhiro Takuma, Toshio Matsuda
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Journal Title
Journal of Pharmacological Sciences
Volume: vol. 118
Pages: 295-298
DOI
Peer Reviewed
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[Journal Article] Activation of metabotropic glutamate 2/3 receptors attenuates methamphetamine-induced hyperlocomotion and increase in prefrontal serotonergic neurotransmission2011
Author(s)
Yukio Ago, Ryota Araki, Koji Yano, Naoki Hiramatsu, Toshiyuki Kawasaki, Shigeyuki Chaki, Atsuro Nakazato, Hirotaka Onoe, Hitoshi Hashimoto, Akemichi Baba, Kazuhiro Takuma, Toshio Matsuda
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Journal Title
Psychopharmacology (Berl)
Volume: vol. 217
Pages: 443-452
DOI
Peer Reviewed
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