Mechanisms of treatment-resistant depression on the basic study of hippocampal neurogenesis in ACTH-treated rats

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590593
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Okayama University
• Principal Investigator: KITAMURA Yoshihisa 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (40423339)
• Co-Investigator(Kenkyū-buntansha): KAWASAKI Hiromu 岡山大学, 大学院・医歯薬学総合研究科, 教授 (60125151) ; ASANUMA Masato 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (00273970)
• Research Collaborator: KOYAMA Toshihiro 岡山大学, 大学院・医歯薬学総合研究科, 助教 (60595106)
• Project Period (FY): 2009 – 2011
• Keywords: 治療抵抗性うつ病 / 電気けいれん療法 / 神経細胞新生 / ドパミン

Research Abstract

We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone(ACTH)-treated rats. The dopamine reuptake inhibitor bupropion and D2/D3 receptor agonist pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. The infusions of bupropion and pramipexole into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. These findings suggest the antidepressant-like effect of bupropion and pramipexole to be related to levels of dopamine in the rat nucleus accumbens.
We previously reported that the chronic administration of ACTH significantly decreased the number of BrdU-positive cells in the subgranular zone of the hippocampal dentate gyrus. This effect was reversed by the coadministration of imipramine and lithium, and electroconvulsive stimuli for 14 days in ACTH-treated rats. These results support the notion that imipramine and lithium, and electroconvulsive stimuli would improve the efficacy of treatment for resistant depression by triggering cell proliferation.

Research Products

• [Journal Article] ACTH反復投与ラットにおける海馬細胞新生の減少及びそのメカニズムに関する検討 (2012)
  • Author(s): 林宏美、土居真穂、尾上由華、鍬塚圭子、三宅彩香、小山敏広、四宮一昭、宮崎育子、浅沼幹人、北村佳久
  • Journal Title: YAKUGAKU ZASSHI Volume: 132 Pages: 173-178
  • Peer Reviewed
• [Journal Article] Chronic treatment with imipramine and lithium increases cell proliferation in the hippocampus in adrenocorticotropic hormone-treated rats (2011)
  • Author(s): Y. Kitamura, M. Doi, K. Kuwatsuka, Y. Onoue, I. Miyazaki, K. Shinomiya, T. Koyama, T. Sendo, H. Kawasaki, M. Asanuma, Y. Gomita
  • Journal Title: Biol. Pharm. Bull Volume: 34 Pages: 77-81
  • Peer Reviewed
• [Journal Article] Effects of bupropion on the forced swim test and release of dopamine in the nucleus accumbens in ACTH-treated rats (2010)
  • Author(s): Y. Kitamura, T Yagi, K. Kitagawa, K. Shinomiya, H. Kawasaki, M. Asanuma, Y. Gomita
  • Journal Title: Naunyn-Schmiedeberg Archives of Pharmacology Volume: 382 Pages: 151-158
  • Peer Reviewed
• [Journal Article] Effects of imipramine and lithium on the suppression of cell proliferation in the dentate gyrus of the hippocampus in ACTH-treated rats (2010)
  • Author(s): M. Doi, I. Miyazaki, T. Nagamachi, K. Shinomiya, H. Matsunaga, T. Sendo, H. Kawasaki, M. Asanuma, Y. Gomita, Y. Kitamura
  • Journal Title: Acta. Med. Okayama Volume: 64 Pages: 219-223
  • Peer Reviewed
• [Journal Article] Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats (2009)
  • Author(s): K. Kitagawa, Y. Kitamura, T. Miyazaki, J. Miyaoka, H. Kawasaki, M. Asanuma, T. Sendo, Y. Gomita
  • Journal Title: Naunyn-Schmiedeberg Archives of Pharmacology Volume: 380 Pages: 59-66
  • Peer Reviewed
• [Presentation] Effects of imipramine and lithium on the suppression of cell proliferation in the dentate gyrus of the hippocampus in ACTH-treated rats (2011)
  • Author(s): K. Kuwatsuka, Y. Onoue, H. Hayashi, M. Doi, T. Koyama, I. Miyazaki, M. Asanuma, Y. Kitamura
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington DC(USA)
  • Year and Date: 2011-11-16
• [Presentation] Effects of electroconvulsive stimuli on neurogenesis in dentate gyrus of ACTH-treated rats (2011)
  • Author(s): T. Koyama, H Hayashi, K. Kuwatsuka, Y. Onoue, M. Doi, I. Miyazaki, M. Asanuma, Y. Kitamura
  • Organizer: Neuroscience 2011
  • Place of Presentation: WashingtonDC(USA)
  • Year and Date: 2011-11-16
• [Presentation] ACTH反復投与ラットにおける海馬細胞新生の減少およびそのメカニズムに関する検討 (2011)
  • Author(s): 林宏美、土井真穂、尾上由華、鍬塚圭子、三宅綾香、小山敏広、四宮一昭、宮崎育子、浅沼幹人、北村佳久
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-29
• [Presentation] ACTH反復投与ラットにおける海馬細胞新生の減少に対するimipramine、lithiumの作用に関する検討 (2011)
  • Author(s): 林宏美、土井真穂、尾上由華、鍬塚圭子、小山敏広、四宮一昭、宮崎育子、浅沼幹人、北村佳久
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-24
• [Presentation] Influence of the suppression of cell proliferation and neurogenesis in the ability of antidepressants in an ACTH-induced animal model of treatment-resistant (2010)
  • Author(s): Y. Kitamura, M. Doi, H. Hayashi, I. Miyazaki, M. Asanuma, H. Kawasaki
  • Organizer: World Pharma 2010
  • Place of Presentation: Copenhagen
  • Year and Date: 2010-07-20
• [Presentation] ACTH反復投与ラットを用いたbupropionの抗うつ効果におけるドパミン神経機能の関与 (2010)
  • Author(s): 八木貴彦、宮崎俊明、北川航平、四宮一昭、浅沼幹人、千堂年昭、北村佳久
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-17
• [Presentation] ACTH反復投与ラットを用いた海馬歯状回における細胞増殖およびアストログリア活性に及ぼす影響 (2010)
  • Author(s): 土居真穂、長町智子、江川真季、宮崎育子、川崎博己、千堂年昭、浅沼幹人、北村佳久
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-17
• [Presentation] Effects of imipramine and lithium on the supression of cell proliferation and neurogenesis of dentate gyrus of hippocampus in ACTH-treated rats (2009)
  • Author(s): M. Doi, I. Miyazaki, K. Shinomiya, M. Asanuma, Y. Kitamura
  • Organizer: The 1st Meeting of Asain College of Neuropsychopharmacology
  • Place of Presentation: Kyoto
  • Year and Date: 2009-11-13
• [Book] 視床下部-下垂体-副腎皮質系過活動モデルを用いた治療抵抗性うつ病モデルの作製および創薬への応用,実験薬理学,実践行動薬理学 (2010)
  • Author(s): 北村佳久、浅沼幹人、宮崎育子、四宮一昭、五味田裕
  • Total Pages: 138-146
  • Publisher: 日本薬理学会金芳堂