Functional develpment of 5-HT/GABA neurons in the raphe nuclei - postnatal stress and epigenetics

• Project/Area Number: 23390284
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hokkaido University
• Principal Investigator: YOSHIOKA Mitsuhiro 北海道大学, 医学(系)研究科(研究院), 教授 (40182729)
• Co-Investigator(Kenkyū-buntansha): IZUMI Takeshi 北海道大学, 医学研究科, 講師 (60312360) ; YOSHIDA Takayuki 北海道大学, 医学研究科, 助教 (60374229) ; OHMURA Yu 北海道大学, 医学研究科, 助教 (80597659) ; KAWATO Suguru 東京大学, 大学院・総合文化研究科, 教授 (50169736)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 精神薬理学 / 幼若期ストレス

Research Abstract

It is known that child abuse is a risk factor for depression. To elucidate the mechanisms and to develop the treatments are required. Rats were subjected to aversive foot shock (FS) during the third week of the postnatal period (3wFS
group). 3wFS group displayed depressive-like behavior in adulthood and showed the increased protein levels of tryptophan hydroxylase 2 in the dorsal raphe nucleus which is a origin of serotonergic neurons. These adverse effects were partly reversed by repeated administration of selective serotonin reuptake inhibitor (SSRI). Thus, it is possible that SSRI administration could partly attenuate the adverse effects of child abuse.

Research Products

• [Journal Article] 扁桃体-up to date 扁桃体の恐怖記憶の分子機構 (2014)
  • Author(s): 吉田隆行 吉岡充弘
  • Journal Title: Clinical Neuroscience 月刊臨床神経科学 Volume: 32（6）
• [Journal Article] Tandospirone Suppresses Impulsive Action by Possible Blockade of the 5-HT_1A Receptor (2013)
  • Author(s): Ohmura Y, Kumamoto H, Tsutsui-Kimura I, Minami M, Izumi T, Yoshida T, Yoshioka M.
  • Journal Title: Journal of Pharmacological Sciences Volume: 122 Issue: 2 Pages: 84-92
  • DOI: 10.1254/jphs.12264FP
  • NAID: 10031185400
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] Milnacipran enhances the control of impulsive action by activating D_1-like receptors in the infralimbic cortex. (2013)
  • Author(s): Tsutsui-Kimura I, Ohmura Y, Izumi T, Kumamoto H, Yamaguchi
  • Journal Title: Psychopharmacology (Berl) Volume: 225 Issue: 2 Pages: 495-504
  • DOI: 10.1007/s00213-012-2835-5
  • Peer Reviewed
• [Journal Article] リチウムの作用機序臨床精神医学 (2013)
  • Author(s): 吉岡充弘
  • Journal Title: Japanese Journal of Clinical Psychiatry Volume: Vol.42No.11 Pages: 1405-1413
• [Journal Article] リチウムの作用機序 (2013)
  • Author(s): 吉岡充弘
  • Journal Title: 臨床精神医学 Volume: 42 Pages: 1405-1413
• [Journal Article] Effects of serotonergic terminal lesion in the amygdala on conditioned fear and innate fear in rats (2012)
  • Author(s): Izumi T, Ohmura Y, Futami Y, Matsuzaki H, Kubo Y, Y oshida T, Y oshioka M
  • Journal Title: Eur J Pharmacol Volume: 696 Issue: 1-3 Pages: 89-95
  • DOI: 10.1016/j.ejphar.2012.09.028
  • Peer Reviewed
• [Journal Article] Distinct neurochemical and functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe nucleus (2012)
  • Author(s): Shikanai H, Y oshida T, Konno K, Y amasaki M, Izumi T, Ohmura Y, Watanabe M, Y oshioka M
  • Journal Title: J Neurosci Volume: 32 Pages: 14415-14426
  • NAID: 120005228624
  • Peer Reviewed
• [Journal Article] Anxiolytic effects of yokukansan, a traditional Japanese medicine, via serotonin 5-HT(1A) receptors on anxiety-related behaviors in rats experienced aversive stress (2012)
  • Author(s): Yamaguchi T, Tsujimatsu A, Kumamoto H, Izumi T, Ohmura Y, Y oshida T, Y oshioka M
  • Journal Title: J Ethnopharmacol Volume: 43 Issue: 2 Pages: 533-539
  • DOI: 10.1016/j.jep.2012.07.007
  • Peer Reviewed
• [Journal Article] 分子精神医学 縫線核(群) (2012)
  • Author(s): 吉岡 充弘
  • Journal Title: 株式会社 先端医学社 Volume: Vol.12 No.4 Pages: 291-294
• [Journal Article] Distinct neurochemical and functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe nucleus. (2012)
  • Author(s): Shikanai H, Yoshida T, Konno K, Yamasaki M, Izumi T, Ohmura Y, Watanabe M, Yoshioka M.
  • Journal Title: Journal of Neuroscience Volume: 32 Issue: 41 Pages: 14415-14426
  • DOI: 10.1523/jneurosci.5929-11.2012
  • NAID: 120005228624
  • Peer Reviewed
• [Journal Article] Behavioral and pharmacological effects of fluvoxamine on decision-making in food patches and the inter-temporal choices of domestic chicks (2012)
  • Author(s): Shohei Matsunami, Yukiko Ogura, Hidetoshi Amita, Takeshi Izumu, Mitsushiro Yoshioka and Toshiya Matsushima
  • Journal Title: Behavioral Brain Research Volume: 233 Issue: 2 Pages: 577-586
  • DOI: 10.1016/j.bbr.2012.05.045
  • Peer Reviewed
• [Journal Article] Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action in rats. (2012)
  • Author(s): Ohmura Y, Tsutsui-Kimura I, Kumamoto H, Minami M, Izumi T.
  • Journal Title: Psychopharmacology (Berl) Volume: 219 Issue: 2 Pages: 148-153
  • DOI: 10.1007/s00213-011-2496-9
  • Peer Reviewed
• [Journal Article] 5-Hydroxytryptophan Attenuates Somatic Signs of Nicotine Withdrawal (2011)
  • Author(s): Ohmura Y, Jutkiewicz EM、Yoshioka M, Domino EF
  • Journal Title: Journal of Pharmacological Sciences Volume: 117 Issue: 2 Pages: 121-124
  • DOI: 10.1254/jphs.11074SC
  • NAID: 10029896243
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Presentation] Repeated milnacipran ameliorates rats with elevated impulsivityミルナシプラン反復投与は衝動性亢進ラットを改善する (2014)
  • Author(s): 木村 生, 大村 優, 吉田隆行, 泉 剛, 吉岡充弘
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台市 仙台国際センタ-
• [Presentation] ミルナシプラン反復投与は衝動性亢進ラットを改善する (2014)
  • Author(s): 木村生、大村 優、吉田隆行、泉 剛、吉岡充弘
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センタ－(仙台市）
• [Presentation] Effects of repeated restrain stress on depression and anxiety like behaviors, andOn glucocorticoid receptor function in the rat brain (2013)
  • Author(s): Robel Ghebreab, Takeshi Izumi, Takayuki Yoshida, Yu Ohmura, Mitsuhiro Yoshioka
  • Organizer: 第129回日本薬理学会関東部会
  • Place of Presentation: 順天堂大学 本郷キャンパス
  • Year and Date: 2013-10-19
• [Presentation] The effects of repeated restrain stress on expression of glucocorticoid receptor and FKBP5 in the brain (2013)
  • Author(s): Robel Ghebreab, Takeshi Izumi, Takayuki Yoshida, Yu Ohmura, MitsuhiroY oshioka
  • Organizer: 第64回日本薬理学会北部会
  • Place of Presentation: 旭川市大雪クリスタルホ-ル
  • Year and Date: 2013-09-13
• [Presentation] 正中縫線核から腹側海馬へのセロトニン神経投射は 5-HT2C 受容体を介して不安様行動を調節する-オプトジェネティクス(光遺伝学)による解明The serotonergic projection from the median raphe nucleus to the ventral hippocampus Modulates anxiety-like behaviorvia stimulating 5-HT2C ewceptors (2013)
  • Author(s): 大村 優, 田中健二, 山中章弘, 吉岡充弘
  • Organizer: 第23回日本臨床精神神経薬理学会 第43回日本神経精神薬理学会合同年会
  • Place of Presentation: 沖縄コンベンションセンタ-
• [Presentation] Effects of hypergravity on serotonin-related gene expression in the mouse brain (2013)
  • Author(s): M.Y oshioka, S.Inubushi, T .Ochiai, M.Mi yamoto, Y .Ohira, H.Ohta
  • Organizer: Palau de Congressons de Catalunya
  • Place of Presentation: スペイン バルセロナ
• [Presentation] 扁桃体におけるセロトニンおよびカンナビノイドシグナル伝達系の相互調節機構 (2013)
  • Author(s): 吉田隆行, 今野幸太郎, 内ヶ島基政, 大村 優, 泉 剛, 渡辺雅彦, 吉岡充弘
  • Organizer: 第36回日本神経科学大会 第56回日本神経化学会大会第23回日本神経回路学会大会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 光遺伝学によるセロトニン神経活動の操作と不安関連行動 (2013)
  • Author(s): 大村 優, 田中謙二, 山中章弘, 吉岡充弘
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 扁桃体におけるセロトニンおよびカンナビノイドシグナル伝達系の相互調節機構 (2013)
  • Author(s): 吉田隆行、今野幸太郎、内ヶ島基政、大村 優、泉 剛、渡辺雅彦、吉岡充弘
  • Organizer: 第36回日本神経科学大会 第56回日本神経化学会大会 第23回日本神経回路学会大会
  • Place of Presentation: 国立京都国際会館(京都市）
• [Presentation] Effects of hypergravity on serotonin-related gene expression in the mouse brain (2013)
  • Author(s): M.Yoshioka,S.Inubushi,T.Ochiai,M.Miyamoto,Y.Ohira,H.Ohta
  • Organizer: 26th ECNP
  • Place of Presentation: Palau de Congressons de Catalunya(ｽﾍﾟｲﾝ ﾊﾞﾙｾﾛﾅ）
• [Presentation] Effects of repeated restrain stress on depression and anxiety like behaviors,and On glucocorticoid receptor function in the rat brain (2013)
  • Author(s): Robel Ghebreab、Takeshi Izumi、Takayuki Yoshida,Yu Ohmura、Mitsuhiro
  • Organizer: 第129回日本薬理学会関東部会
  • Place of Presentation: 順天堂大学本郷ｷｬﾝﾊﾟｽ(東京都）
• [Presentation] 正中縫線核から腹側海馬へのセロトニン神経投射は5-HT2C受容体を介して不安様行動 (2013)
  • Author(s): 大村 優、田中健二、山中章弘、吉岡充弘
  • Organizer: 第23回日本臨床精神神経薬理学会 第43回日本神経精神薬理学会合同年会
  • Place of Presentation: 沖縄コンベンションセンタ－(宜野湾市）
• [Presentation] 3-コンパ－トメント装置を用いての社会性・不安の行動薬理学的評価法 (2013)
  • Author(s): 神宮司華子、山口 拓、福森 良、吉岡充弘、山本経之
  • Organizer: 第66回日本薬理学会西南部会
  • Place of Presentation: 福岡大学(福岡市）
• [Presentation] 光遺伝学によるセロトニン神経活動の操作と不安関連行動 (2013)
  • Author(s): 大村 優
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場(福岡県）
• [Presentation] Tandospirone supptrsses impulsive action in rats (2012)
  • Author(s): Yu Ohmura, Haruko Kumamoto, Iku Tsusui-Kimura, Takeshi Izumi, Takayuki Yoshida, Mitsuhiro Yoshioka
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都大学(京都)
  • Year and Date: 2012-03-16
• [Presentation] Optogenetic Control of Serotonergic Neurons and Anxiety-like Behavior (2012)
  • Author(s): Yu Ohmura, Kenji Tanaka, Akihiro Yamanaka, Mitsuhiro Yoshioka
  • Organizer: ACNP 51st Annual Meeting
  • Place of Presentation: 米国Westin Dipromat in Hollyseed
• [Presentation] Effects of Parabolic Flight on Serotonin-Related Gene Expression in theMouse Brain (2012)
  • Author(s): MitsuhiroY oshioka, TakuY amaguchi, Hi sashiOhta, JyunichiroGyotoku, Mutsum I Miyamoto and T oshimasa Ochiai
  • Organizer: The21stKOREA-JAP ANJOINT SEMINAR ON PHARMACOLOGY
  • Place of Presentation: 韓国 済州島 Shine Ville Luxury Resort Jeju
• [Presentation] SSRI exerts anxiolytic effect via 5-HT1A receptors in the basolateral nucleus of amygdala (2012)
  • Author(s): Takeshi Izumi, Takayuki Yoshida, Hirokazu Matsuzaki, Kotaro Konno, Kenji F . Tanaka, Hiroki Shikanai, Y u Ohmura, MasahikoWatanabe, Mitsuhiro Yoshioka
  • Organizer: Neuroscience 2012 米国 ニュ-オ-リンズ
  • Place of Presentation: Ernest N.Morial Convention Center
• [Presentation] 腹側海馬におけるセロトニン-7 受容体は恐怖記憶の想起に関与しているSerotonin-7(5-HT7) receptor in the ventral hippocampus is involved in the Retrieval of fear memory (2012)
  • Author(s): 大村 優, 吉田隆行, 泉 剛, 吉岡充弘
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: Neuroscience 2012 名古屋国際会議場
• [Presentation] Acute administration of lithium, but not valproic acid or carbamazepine, suppresses impulsive action in rats (2012)
  • Author(s): Yu Ohmura, Mitsuhiro Yoshioka
  • Organizer: 第2回東アジア双極性研究会 The 2ND MEETING OF EAST ASIAN BIPOLAR FORUM
  • Place of Presentation: 九州大学
• [Presentation] Functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe nucleus (2012)
  • Author(s): Mitsuhiro Yoshioka Hiroki Shikanai, Takayuki Yoshida, Kohtarou Konnno
  • Organizer: Serotonin CLUB MEETING
  • Place of Presentation: フランスモンペリエ
• [Presentation] SSRI exerts anxiolytic effect via 5-HT1A receptors in the basolateral nucleus of amygdala (2012)
  • Author(s): Izumi T
  • Organizer: Society for Neuroscience 42nd Annual Meeting
  • Place of Presentation: Ernest N/Morial Convention Center(USA)
• [Presentation] Effects of Parabolic Flight on Serotonin-Related Gene Expression in the Mouse Brain (2012)
  • Author(s): Mitsuhiro Yoshioka
  • Organizer: The 21st KOREA-JAPAN JOINT SEMINAR ON PHARMACOLOGY
  • Place of Presentation: Shine Ville Luxury Resort Jeju(韓国）
• [Presentation] 扁桃体における不安発現に対する5-HT作動性神経の調節メカニズム (2011)
  • Author(s): 泉剛、吉岡充弘
  • Organizer: 第21回日本臨床精神薬理学会第41回日本神経精神薬理学会年会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2011-10-27
• [Presentation] 背側縫線核におけるGABA合成酸素GAD67含有5-HT作動性ニューロンの細胞特性 (2011)
  • Author(s): 鹿内浩樹、吉田隆行、今野幸太郎、泉剛、大村優、渡邉雅彦、吉岡充弘
  • Organizer: 第62回日本薬理学会北部会
  • Place of Presentation: 江陽グランドホテル(宮城)
  • Year and Date: 2011-09-29
• [Presentation] パラボリック飛行時の血中ストレスマーカ- (2011)
  • Author(s): 吉岡充弘、山口拓、行徳純一郎、落合俊昌、太田尚
  • Organizer: 第15回活性アミンに関するワークショップ
  • Place of Presentation: 徳島文理大学国際会議場(徳島)
  • Year and Date: 2011-08-11
• [Presentation] Effect of parabo 1 ic flight on plasma arginine vasopressin as a sensitive marker for psychophysiological stress in humans (2011)
  • Author(s): M.Yoshioka、T Yamaguchi, J.Gyotoku, T.Ochiaiand, H.Ohta
  • Organizer: Experimental Biology 2011
  • Place of Presentation: Walter E.Washington Convwntion Center (米国)
  • Year and Date: 2011-04-11
• [Book] Role of the amygdalarserotonergic system in emotional regulation and disorders, In:Insights into the Amygdala, chapter 2 (2012)
  • Author(s): Izumi T , Yoshida T, Watanabe M, Yoshioka M
  • Publisher: Nova Science Publishers, Inc
• [Book] 不安恐怖, 『心理学研究法 3』学習・動機・情動 (2011)
  • Author(s): 山口 拓, 富樫廣子, 吉岡充弘
  • Publisher: 誠信堂
• [Book] 第8章「不安・恐怖」、心理学研究法3-学習・動機・情動 (2011)
  • Author(s): 吉岡充弘、山口拓、富樫廣子
  • Publisher: 誠信書房
• [Remarks]
  • URL: http://hokudaineuropharmacol.com