Papers - TADOKORO SHIGENORI

G protein-coupled receptor kinase 6/-arrestin 2 system in a rat model of dopamine supersensitivity psychosis

Yasunori, Oda, Shigenori Tadokoro, Masayuki Takase, Nobuyuki Kanahara, Hiroyuki Watanabe, Yukihiko Shirayama, Kenji Hashimoto, Masaomi Iyo

JOURNAL OF PSYCHOPHARMACOLOGY   29 ( 12 ) 1308 - 1313  2015.12  [Refereed]

DOI PubMed J-GLOBAL

An Introduction to “The Emptiness Theory of Brain” : Suggestion of a New Version of Type Identity Theory

Shigenori Tadokoro

哲学・科学史論叢 ( 東京大学教養学部哲学・科学史部会 )  17 ( 第十七号 ) 17 - 39  2015.01  [Refereed]

Authorship：   Lead author  , Corresponding author

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「人間を人間たらしめる心の働き」と「脳」の新しい関係を提唱することを目指した哲学論文。精神医学や認知神経科学において前提とされている両者の関係を批判的に検討した上で、心の働きを、語り行動を中心とした全身の身体活動と同一とみなす、「自分語り同一説」という心身問題上の立場を提唱した。さらに、こうした立場から、「自分語りする動物」という新しい有用な人間観を提唱した。

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Optimal Extent of Dopamine D2 Receptor Occupancy by Antipsychotics for Treatment of Dopamine Supersensitivity Psychosis and Late-Onset Psychosis

Masaomi Iyo, Shigenori Tadokoro, Nobuhisa Kanahara, Tasuku Hashimoto, Tomihisa Niitsu, Hiroyuki Watanabe, Kenji Hashimoto

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY ( LIPPINCOTT WILLIAMS & WILKINS )  33 ( 3 ) 398 - 404  2013.06  [Refereed]

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Several studies have proposed an optimal dopamine D2 receptor occupancy by antipsychotics (OOc) to establish optimal pharmacological treatment of schizophrenia. However, there are limitations to the use of the OOc, especially in application to patients with treatment-resistant schizophrenia, including dopamine supersensitivity psychosis (DSP) or late-onset psychosis (LOP). It has been suggested that D2 receptor density is up-regulated by chronic treatment of antipsychotics in DSP, whereas it may be low in LOP owing to age-related reduction. In estimation of the proposed OOc, these alterations have not been taken into account, which may be one of the factors contributing to the limited application of this index. We here hypothesize that there is an optimal range in the number of D2 receptors available for dopamine binding to elicit adequate neurotransmission in the treatment of patients with schizophrenia. We then estimated the OOc under the assumption that the range is constant while D2 density is variable. The results showed that the OOc and plasma level of antipsychotics increase with an increase in the D2 density but decrease with a decrease in the D2 density. That is, if the range of OOc is 65% to 78% in a standard D2 density, it becomes 82% to 89% under 2-fold up-regulated density and 42% to 63% under a 40% reduced density. The results also indicated that the reduction of the plasma antipsychotic level is greater during a given time period in patients with higher D2 density, as they need a higher antipsychotic dose to achieve the raised OOc, which would account for the clinical features of DSP, for example, acute exacerbation after a discontinuation of antipsychotics. On the other hand, in patients with lower D2 density, only a lower antipsychotic dose will achieve the OOc, and a small increase in the dose will result in a greater increase in occupancy and induce extrapyramidal adverse effects more easily. Furthermore, the reduction of the plasma antipsychotic level during the time period is smaller, which prolongs extrapyramidal adverse effects after discontinuation of antipsychotics in LOP. We also attempted to develop a strategy for the prevention and treatment of patients with DSP or LOP by focusing on D2 density.

DOI PubMed J-GLOBAL

Aripiprazole as "dopamine sensitivity stabilizer".

Shigenori Tadokoro

Nihon rinsho. Japanese journal of clinical medicine ( 4 )  71 ( 4 ) 684 - 688  2013.04  [Invited]

Authorship：   Lead author  , Corresponding author

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新規抗精神病薬の一つであり、部分アゴニスト（Partial Agonist）という特殊な薬理学的特徴をもつアリピプラゾールが、「ドパミン感受性安定薬（Dopamine Sensitivity Stabilizer）」として働くことで、統合失調症患者における精神病症状の再燃・増悪を予防できる可能性があることを、筆者自身による動物実験と、体験した症例に基づいて提唱した。

PubMed CiNii

The methodological foundation of psychotherapy: From the viewpoint of "Philosophy of Psychiatry"

Shigenori Tadokoro

修士学位論文（東京大学大学院 総合文化研究科）    2013.01  [Refereed]

Authorship：   Lead author  , Corresponding author

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言語的介入を主体とした精神療法という、一見非科学的にも見える治療行為を、科学的な治療としてどのように位置づけたらいいのかについて、最近興隆しつつある精神医学基礎論（Philosophy of Psychiatry）という分野の成果に依拠して考察した。その過程で、私たち人間の語り行動は、その言語的内容が他の言語的内容と意味的（合理的）関係を取り結ぶとともに、語りそのものが他の行動と因果関係をもつことに注目し、「語り行動モデル」と呼ぶ心のモデルを提唱した。

Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

Shigenori Tadokoro, Naoe Okamura, Yoshimoto Sekine, Nobuhisa Kanahara, Kenji Hashimoto, Masaomi Iyo

SCHIZOPHRENIA BULLETIN ( OXFORD UNIV PRESS )  38 ( 5 ) 1012 - 1020  2012.09  [Refereed]

Authorship：   Lead author  , Corresponding author

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Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D-2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pre-treated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D-2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D-2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D-2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D-2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D-2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia.

DOI PubMed J-GLOBAL

Infusions of Allopregnanolone Into the Hippocampus and Amygdala, but not Into the Nucleus Accumbens and Medial Prefrontal Cortex, Produce Antidepressant Effects on the Learned Helplessness Rats

Yukihiko Shirayama, Katsumasa Muneoka, Makoto Fukumoto, Shigenori Tadokoro, Goro Fukami, Kenji Hashimoto, Masaomi Iyo

HIPPOCAMPUS ( WILEY-BLACKWELL )  21 ( 10 ) 1105 - 1113  2011.10  [Refereed]

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Patients with depression showed a decrease in plasma and cerebrospinal fluid allopregnanolone (ALLO). But antidepressants increased the contents of ALLO in the rat brain. We examined the antidepressant-like effects of infusion of ALLO into the cerebral ventricle, hippocampus, amygdala, nucleus accumbens, or prefrontal cortex of learned helplessness (LH) rats (an animal model of depression). Of these regions, infusions of ALLO into the cerebral ventricle, the CA3 region of hippocampus, or the central region of amygdala exerted antidepressant-like effects. Infusion of ALLO into the hippocampal CA3 region or the central amygdala did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. It is well documented that ALLO exerts its effects through GABA receptors. Therefore, we examined the antagonistic effects of flumazenil (a GABA receptor antagonist) on the antidepressant-like effects of ALLO. Coinfusion of flumazenil with ALLO into the hippocampal CA3 region, but not into the central amygdala, blocked the antidepressant-like effects of ALLO. However, coinfusion of (1) MK801 (an NMDA receptor antagonist), but not cycloheximide (a protein synthesis inhibitor), blocked the antidepressant-like effects of ALLO in the central amygdala. These results suggest that ALLO exerts antidepressant-like effects in the CA3 region of hippocampus through the GABA system and in the central region of amygdala, dependently on the activation of the glutamatergic mechanisms. (C) 2010 Wiley-Liss, Inc.

DOI PubMed J-GLOBAL

Fluvoxamine may prevent onset of psychosis: a case report of a patient at ultra-high risk of psychotic disorder

Shigenori Tadokoro, Nobuhisa Kanahara, Shuichi Kikuchi, Kenji Hashimoto, Masaomi Iyo

ANNALS OF GENERAL PSYCHIATRY   10  2011.09  [Refereed]

Authorship：   Lead author  , Corresponding author

DOI PubMed J-GLOBAL

On the Change of "Motivation" and "Externalization of Disorder" through the Cognitive-behavioural Psychotherapy : A case study of the hospitalized treatment for a patient with anorexia nervosa

田所重紀, 中里道子, 白石哲也, 伊豫雅臣

認知療法研究 ( 日本認知療法学会 )  3   98 - 106  2010.09  [Refereed]

Authorship：   Lead author  , Corresponding author

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神経性無食欲症に罹患した23歳の女性に対し、認知行動療法を主体とした入院治療を施行した症例報告。約1年に及ぶ入院治療の経過で得られた患者の発言内容に注目し、そこから「治療に対する動機づけ」と「疾病の外在化」の程度を定量化して両者の関係を調べ、その密接な関連性について様々な角度から考察した。

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