Effects of antipsychotic drugs on pre-and postsynaptic dopaminergic functions measured by PET

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591587
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: ITO Hiroshi 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, プログラムリーダー (20360357)
• Co-Investigator(Kenkyū-buntansha): TAKANO Harumasa 放射線医学総合研究所, 分子イメージング研究センター, 室長 (30348792) ; TAKAHASHI Hidehiko 放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (60415429)
• Co-Investigator(Renkei-kenkyūsha): ARAKAWA Ryosuke 放射線医学総合研究所, 分子イメージング研究センター, 博士研究員 (40350095)
• Project Period (FY): 2009 – 2011
• Keywords: PET / 向精神薬 / 抗精神病薬 / ドーパミン / ドーパミン受容体

Research Abstract

Effects of antipsychotic drugs have been considered to be mediated by modulation of postsynaptic dopamine D2 receptors. To investigate the effects of antagonist or partial agonist antipsychotics on presynaptic functions of dopaminergic neurotransmission, changes in dopamine synthesis capacity by antipsychotics, risperidone or aripiprazole, were measured by PET in healthy men. For both antipsychotics, significant negative correlations were observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by antipsychotics, indicating that these antipsychotics can be assumed to stabilize the dopamine synthesis capacity.

Research Products

• [Journal Article] 脳神経PETと治療戦略.核医学検査の新しい展開～治療戦略への応用 (2011)
  • Author(s): 伊藤浩
  • Journal Title: 映像情報メディカル Volume: Vol.43 Pages: 850-854
• [Journal Article] Relation between presynaptic and postsynaptic dopaminergic functions measured by positron emission tomography : implication of dopaminergic tone (2011)
  • Author(s): Ito H, Kodaka F, Takahashi H, Takano H, Arakawa R, Shimada H, Suhara T
  • Journal Title: J Neurosci Volume: Vol.31 Pages: 7886-7890
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  • Peer Reviewed
• [Journal Article] Serotonergic neurotransmission in the living human brain : A positron emission tomography study using[^<11> C] DASB and[^<11> C] WAY100635 in young healthy men (2011)
  • Author(s): Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Kodaka F, Otsuka T, Kato M, Suhara T
  • Journal Title: Synapse Volume: Vol.65 Pages: 624-633
  • URL: http://onlinelibrary.wiley.com/doi/10.1002/syn.20883/abstract?systemMessage=Wiley+Online+Library+will+be+disrupted+on+9+June+from+10%3A00-12%3A00+BST+%2805%3A00-07%3A00+EDT%29+for+essential+maintenance
  • Peer Reviewed
• [Journal Article] Effect of risperidone on high-affinity state of dopamine D_2 receptors : a PET study with agonist ligand[^<11> C](R)-2-CH3O-N-n-propylnorapomorphine (2011)
  • Author(s): Kodaka F, Ito H, Takano H, Takahashi H, Arakawa R, Miyoshi M, Okumura M, Otsuka T, Nakayama K, Halldin C, Farde L, Suhara T
  • Journal Title: Int J Neuropsychopharmacol Volume: Vol.14 Pages: 83-89
  • URL: http://journals.cambridge.org/action/displayAbstract?fromPage=online & aid=7928662
  • Peer Reviewed
• [Journal Article] PETの新しい活用法-抗精神病薬開発における有用性- (2010)
  • Author(s): 伊藤浩
  • Journal Title: Isotope News Volume: Vol.10(No.678) Pages: 2-5
• [Journal Article] 脳疾患における分子イメージング核医学による脳病態の観察 (2010)
  • Author(s): 伊藤浩
  • Journal Title: 臨床放射線 Volume: Vol.55 Pages: 483-486
• [Journal Article] Quantitative analysis of dopamine transporters in human brain using[11C] PE2I and positron emission tomography : evaluation of reference tissue models (2010)
  • Author(s): Seki C, Ito H, Ichimiya T, Arakawa R, Ikoma Y, Shidahara M, Maeda J, Takano A, Takahashi H, Kimura Y, Suzuki K, Kanno I, Suhara T
  • Journal Title: Ann Nucl Med Volume: Vol.24 Pages: 249-260
  • URL: http://www.springerlink.com/content/7680221811nv4rlw/
  • Peer Reviewed
• [Journal Article] Positron emission tomography inter-scanner differences in dopamine D_2 receptor binding measured with[^<11> C] FLB457 (2010)
  • Author(s): Kodaka F, Ito H, Shidahara M, Takano H, Takahashi H, Arakawa R, Nakayama K, Suhara T
  • Journal Title: Ann Nucl Med Volume: Vol.24 Pages: 671-677
  • URL: http://www.springerlink.com/content/m70604270017g456/
  • Peer Reviewed
• [Journal Article] Measurement of dopamine D2 receptors in living human brain using[11C] raclopride with ultra-high specific radioactivity (2010)
  • Author(s): Fujimura Y, Ito H, Takahashi H, Yasuno F, Ikoma Y, Zhang MR, Nanko S, Suzuki K, Suhara T
  • Journal Title: Nucl Med Biol Volume: Vol.37 Pages: 831-835
  • URL: http://www.sciencedirect.com/science/article/pii/S0969805110002283
  • Peer Reviewed
• [Journal Article] Positron emission tomography measurement of dopamine D_2 receptor occupancy in the pituitary and cerebral cortex : relation to antipsychotic-induced hyperprolactinemia (2010)
  • Author(s): Arakawa R, Okumura M, Ito H, Takano A, Takahashi H, Takano H, Maeda J, Okubo Y, Suhara T
  • Journal Title: J Clin Psychiatry Volume: Vol.71 Pages: 1131-1137
  • URL: http://article.psychiatrist.com/dao_1-login.asp?ID=10006739 & RSID=16946401171139
  • Peer Reviewed
• [Journal Article] Extrastriatal dopamine D2 receptor occupancy in olanzapine-treated patients with schizophrenia (2010)
  • Author(s): Arakawa R, Ito H, Okumura M, Takano A, Takahashi H, Takano H, Okubo Y, Suhara T
  • Journal Title: Eur Arch Psychiatry Clin Neurosci Volume: Vol.260 Pages: 345-350
  • URL: http://www.springerlink.com/content/d15876721x0tqx19/
  • Peer Reviewed
• [Journal Article] Dopamine D_2 receptor occupancy by perospirone : a positron emission tomography study in patients with schizophrenia and healthy subjects (2010)
  • Author(s): Arakawa R, Ito H, Takano A, Okumura M, Takahashi H, Takano H, Okubo Y, Suhara T
  • Journal Title: Psychopharmacology(Berl) Volume: Vol.209 Pages: 285-290
  • URL: http://www.springerlink.com/content/j7038357525x8677/
  • Peer Reviewed
• [Journal Article] Measurement error analysis for the determination of dopamine D_2 receptor occupancy using the agonist radioligand[^<11> C] MNPA (2010)
  • Author(s): Shidahara M, Ito H, Otsuka T, Ikoma Y, Arakawa R, Kodaka F, Seki C, Takano H, Takahashi H, Turkheimer FE, Kimura Y, Kanno I, Suhara T
  • Journal Title: J Cereb Blood Flow Metab Volume: Vol.30 Pages: 187-195
  • URL: http://www.nature.com/jcbfm/journal/v30/n1/full/jcbfm2009193a.html
  • Peer Reviewed
• [Journal Article] A new graphic plot analysis for determination of neuroreceptor binding in positron emission tomography studies (2010)
  • Author(s): Ito H, Yokoi T, Ikoma Y, Shidahara M, Seki C, Naganawa M, Takahashi H, Takano H, Kimura Y, Ichise M, Suhara T
  • Journal Title: Neuroimage Volume: Vol.49 Pages: 578-586
  • URL: http://www.sciencedirect.com/science/article/pii/S1053811909007915
  • Peer Reviewed
• [Journal Article] Effects of the antipsychotic risperidone on dopamine synthesis in human brain measured by positron emission tomography with L-[β-^<11> C] DOPA : a stabilizing effect for dopaminergic neurotransmission? (2009)
  • Author(s): Ito H, Takano H, Takahashi H, Arakawa R, Miyoshi M, Kodaka F, Okumura M, Otsuka T, Suhara T
  • Journal Title: J Neurosci Volume: Vol.29 Pages: 13730-13734
  • URL: http://www.jneurosci.org/content/29/43/13730.long
  • Peer Reviewed
• [Journal Article] Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with^<11> C-AC-5216 (2009)
  • Author(s): Miyoshi M, Ito H, Arakawa R, Takahashi H, Takano H, Higuchi M, Okumura M, Otsuka T, Kodaka F, Sekine M, Sasaki T, Fujie S, Seki C, Maeda J, Nakao R, Zhang MR, Fukumura T, Matsumoto M, Suhara T
  • Journal Title: J Nucl Med Volume: Vol.50 Pages: 1095-1101
  • URL: http://jnm.snmjournals.org/content/50/7/1095.long
  • Peer Reviewed
• [Journal Article] Increase in thalamic binding of[^<11> C] PE2I in patients with schizophrenia : a positron emission tomography study of dopamine transporter (2009)
  • Author(s): Arakawa R, Ichimiya T, Ito H, Takano A, Okumura M, Takahashi H, Takano H, Yasuno F, Kato M, Okubo Y, Suhara T
  • Journal Title: J Psychiatr Res Volume: Vol.43 Pages: 1219-1223
  • URL: http://www.sciencedirect.com/science/article/pii/S0022395609000892
  • Peer Reviewed
• [Journal Article] Quantitative PET analysis of the dopamine D_2 receptor agonist radioligand^<11> C-(R)-2-CH3O-N-n-propylnorapomorphine in the human brain (2009)
  • Author(s): Otsuka T, Ito H, Halldin C, Takahashi H, Takano H, Arakawa R, Okumura M, Kodaka F, Miyoshi M, Sekine M, Seki C, Nakao R, Suzuki K, Finnema S, Hirayasu Y, Suhara T, Farde L
  • Journal Title: J Nucl Med Volume: Vol.50 Pages: 703-710
  • URL: http://jnm.snmjournals.org/content/50/5/703.long
  • Peer Reviewed
• [Journal Article] No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans : a positron emission tomography study (2009)
  • Author(s): Ito H, Arakawa R, Takahashi H, Takano H, Okumura M, Otsuka T, Ikoma Y, Shidahara M, Suhara T
  • Journal Title: Int J Neuropsychopharmacol Volume: Vol.12 Pages: 667-675
  • URL: http://journals.cambridge.org/action/displayAbstract?fromPage=online & aid=5564868
  • Peer Reviewed
• [Journal Article] Regional dopamine synthesis in patients with schizophrenia using L-[β-^<11> C] DOPA PET (2009)
  • Author(s): Nozaki S, Kato M, Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Fujimura Y, Matsumoto R, Ota M, Takano A, Otsuka A, Yasuno F, Okubo Y, Kashima H, Suhara T
  • Journal Title: Schizophr Res Volume: Vol.108 Pages: 78-84
  • URL: http://www.sciencedirect.com/science/article/pii/S092099640800515X
  • Peer Reviewed
• [Journal Article] Improvement of likelihood estimation in Logan graphical analysis using maximum a posteriori for neuroreceptor PET imaging (2009)
  • Author(s): Shidahara M, Seki C, Naganawa M, Sakata M, Ishikawa M, Ito H, Kanno I, Ishiwata K, Kimura Y
  • Journal Title: Ann Nucl Med Volume: Vol.23 Pages: 163-171
  • URL: http://www.springerlink.com/content/f871160t8743p662/?MUD=MP
  • Peer Reviewed
• [Journal Article] Neuroimaging and physiological evidence for involvement of glutamatergic transmission in regulation of the striatal dopaminergic system (2009)
  • Author(s): Tokunaga M, Seneca N, Shin RM, Maeda J, Obayashi S, Okauchi T, Nagai Y, Zhang MR, Nakao R, Ito H, Innis RB, Halldin C, Suzuki K, Higuchi M, Suhara T
  • Journal Title: J Neurosci Volume: Vol.12 Pages: 1887-1896
  • URL: http://www.jneurosci.org/content/29/6/1887.long
  • Peer Reviewed
• [Presentation] 核医学(1)脳:変性疾患(認知症等) (2011)
  • Author(s): 伊藤浩
  • Organizer: 第47回日本医学放射線学会秋季臨床大会
  • Place of Presentation: 下関市
  • Year and Date: 20111021-23
• [Presentation] 神経放射線における分子イメージングの可能性 (2011)
  • Author(s): 伊藤浩
  • Organizer: 第40回日本神経放射線学会
  • Place of Presentation: 東京都品川区
  • Year and Date: 20110224-26
• [Presentation] 核医学;脳 (2011)
  • Author(s): 伊藤浩
  • Organizer: 第22回放射線科認定医試験講習会
  • Place of Presentation: 東京都板橋区
  • Year and Date: 2011-07-13
• [Presentation] ドーパミン作動性神経系における前シナプス機能と後シナプス機能の関係 (2010)
  • Author(s): 伊藤浩、高橋英彦、高野晴成、荒川亮介、小高文聰、須原哲也
  • Organizer: 第50回日本核医学会学術総会
  • Place of Presentation: さいたま市
  • Year and Date: 20101111-13
• [Presentation] 脳機能イメージング. PETによる脳機能イメージング (2010)
  • Author(s): 伊藤浩
  • Organizer: 第29回日本医用画像工学会大会
  • Place of Presentation: 神奈川県伊勢原市
  • Year and Date: 20100730-31
• [Presentation] Relation between pre-and postsynaptic dopaminergic functions measured by PET : implication of dopaminergic tone (2010)
  • Author(s): Ito H, Takahashi H, Takano H, Arakawa R, Kodaka F, Suhara T
  • Organizer: The Eighth International Symposium on Functional Neuroreceptor Mapping of Living Brain(Neuroreceptor Mapping 2010)
  • Place of Presentation: Glasgow, UK
  • Year and Date: 20100722-24
• [Presentation] 抗精神病薬による脳内ドーパミン生成能変化の検討 (2009)
  • Author(s): 伊藤浩、高野晴成、高橋英彦、荒川亮介、小高文聰、須原哲也
  • Organizer: 第49回日本核医学会学術総会
  • Place of Presentation: 旭川市
  • Year and Date: 20091001-03
• [Presentation] 脳疾患における分子イメージング-緒言:核医学による脳病態の観察 (2009)
  • Author(s): 伊藤浩、岡沢秀彦
  • Organizer: 第49回日本核医学会学術総会
  • Place of Presentation: 旭川市
  • Year and Date: 20091001-03
• [Presentation] Effects of second-generation antipsychotic drug on dopamine synthesis in human brain measured by PET with L-[C-11] DOPA (2009)
  • Author(s): Ito H, Takano H, Takahashi H, Arakawa R, Miyoshi M, Kodaka F, Okumura M, Otsuka T, Suhara T
  • Organizer: XXIVth International Symposium on Cerebral Blood Flow Metabolism and Function(BRAIN' 09) & IXth International Conference on Quantification of Brain Function with PET(BRAIN PET' 09)
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 20090629-0703
• [Presentation] Effects of antipsychotic drug on dopamine synthesis in humans measured by PET with[C-11] DOPA (2009)
  • Author(s): Ito H, Takano H, Takahashi H, Arakawa R, Suhara T
  • Organizer: The Society of Nuclear Medicine 56st Annual Meeting
  • Place of Presentation: Toronto, Ontario, Canada
  • Year and Date: 20090613-17
• [Presentation] Effects of psychotropic drugs on neurotransmission system measured by PET (2009)
  • Author(s): Ito H
  • Organizer: 2009 Taiwan Neuroscience Symposium "Diagnosis, Treatment and Adherence"
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2009-12-05
• [Presentation] 脳分子イメージングの最前線-分子イメージングによる精神神経疾患の病態評価 (2009)
  • Author(s): 伊藤浩
  • Organizer: PETサマーセミナー2009 inお台場
  • Place of Presentation: 東京都江東区
  • Year and Date: 2009-08-30
• [Presentation] 脳神経伝達機能の分子イメージング (2009)
  • Author(s): 伊藤浩
  • Organizer: 金沢大学十全医学会学術集会「分子イメージング」
  • Place of Presentation: 金沢市
  • Year and Date: 2009-07-25
• [Book] 遺伝子医学MOOK 18号創薬研究への分子イメージング応用 (2011)
  • Author(s): 伊藤浩
  • Total Pages: 218
  • Publisher: メディカルドゥ
• [Book] ドーパミン神経伝達系分子プローブとそのイメージング-臨床医とコメディカルのための最新クリニカルPET (2010)
  • Author(s): 伊藤浩
  • Total Pages: 427
  • Publisher: 先端医療技術研究所
• [Remarks]
  • URL: http://www.nirs.go.jp/research/division/mic/group/g_sentan-seitai.html
• [Remarks]
  • URL: http://www.nirs.go.jp/research/division/mic/group/t_nou-byotai.html