Neural and pharmacological mechanism of drug addiction through negative reinforcement

• Project/Area Number: 17KK0074
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Experimental psychology
• Research Institution: Waseda University
• Principal Investigator: Kosaki Yutaka 早稲田大学, 文学学術院, 教授 (80738469)
• Project Period (FY): 2018 – 2021
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
• Keywords: 依存 / 連合学習 / 覚せい剤 / 道具的行動 / 負の強化 / 相反過程 / 条件性補償反応 / 動物 / 薬物依存 / 超音波発声 / 習慣 / 強迫性 / ギャンブル行動 / メタンフェタミン / ニコチン / 道具的条件づけ / パヴロフ型条件づけ

Outline of Final Research Achievements

The current research project explored learning processes that contribute to drug addiction, with a particular focus on the process of negative reinforcement. From the results of individual experiments using rats and mice, it has been demonstrated that drugs of abuse disrupt normal decision making, and that repeated exposures to methamphetamine come to elicit context-dependent ultra sonic vocalisations (USVs). The conditioned USVs could serve as a convenient behavioural measure to capture the development of compensatory response to drug-paired cue, which has been given theoretical importance in the account of drug addiction through negative reinforcement process. Furthermore, the results also offered important insights into how once-extinguished instrumental behaviour re-emerge after contextual change. Overall, the current research project gave rise to a set of important empirical findings which could advance our understanding of drug addiction.

Academic Significance and Societal Importance of the Research Achievements

薬物依存やギャンブル・インターネットなどに対する依存・行動嗜癖は社会的に極めて大きな問題であり、現在その解決について糸口が見えないような深刻な状態である。本研究では、依存に関して学習理論の立場からその機序解明に向けて動物を用いた基礎的研究を実施した。本研究からは、依存を支える心理・行動過程についていくつかの重要な知見が得られた。これは依存に関する理論的な説明を進展させるのみならず、社会応用的にも依存の治療・再発防止に向けて手がかりを与える重要な意義を持つと考えられる。

Research Products

• [Int'l Joint Research] ケンブリッジ大学(英国) (2019)
  • Year and Date: 2019-03-26
• [Journal Article] Measurement of the exploration?exploitation response of dogs through a concurrent visual discrimination task (2022)
  • Author(s): Shinoda Kumi、Kosaki Yutaka、Nagasawa Miho、Kikusui Takefumi
  • Journal Title: Behavioural Processes Volume: 199 Pages: 104644-104644
  • DOI: 10.1016/j.beproc.2022.104644
  • Peer Reviewed / Open Access
• [Journal Article] Higher-Order Conditioning in the Spatial Domain (2021)
  • Author(s): Bouchekioua Youcef、Kosaki Yutaka、Watanabe Shigeru、Blaisdell Aaron P.
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 15 Pages: 1-7
  • DOI: 10.3389/fnbeh.2021.766767
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spatial inference without a cognitive map: the role of higher‐order path integration (2020)
  • Author(s): Bouchekioua Youcef、Blaisdell Aaron P.、Kosaki Yutaka、Tsutsui‐Kimura Iku、Craddock Paul、Mimura Masaru、Watanabe Shigeru
  • Journal Title: Biological Reviews Volume: 96 Issue: 1 Pages: 52-65
  • DOI: 10.1111/brv.12645
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Spontaneous object-location memory based on environmental geometry is impaired by both hippocampal and dorsolateral striatal lesions (2020)
  • Author(s): Poulter Steven L.、Kosaki Yutaka、Sanderson David J.、McGregor Anthony
  • Journal Title: Brain and Neuroscience Advances Volume: 4 Pages: 1-4
  • DOI: 10.1177/2398212820972599
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] En route to delineating hippocampal roles in spatial learning (2019)
  • Author(s): Poulter, S., Austen, J. M., Kosaki, Y., Dachtler, J., Lever, C., & McGregor, A.
  • Journal Title: Behavioural brain research Volume: 369 Pages: 111936-111936
  • DOI: 10.1016/j.bbr.2019.111936
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The response strategy and the place strategy in a plus-maze have different sensitivities to devaluation of expected outcome (2018)
  • Author(s): Kosaki Yutaka、Pearce John M.、McGregor Anthony
  • Journal Title: Hippocampus Volume: 28 Issue: 7 Pages: 484-496
  • DOI: 10.1002/hipo.22847
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Striatonigral direct pathway activation is sufficient to induce repetitive behaviors (2017)
  • Author(s): Bouchekioua Youcef、Tsutsui-Kimura Iku、Sano Hiromi、Koizumi Miwako、Tanaka Kenji F.、Yoshida Keitaro、Kosaki Yutaka、Watanabe Shigeru、Mimura Masaru
  • Journal Title: Neuroscience Research Volume: 17 Pages: 30454-30456
  • DOI: 10.1016/j.neures.2017.09.007
  • Peer Reviewed
• [Presentation] Development of ultrasonic vocalizations to methamphetamine-associated cue in the absence of the drug: a conditioned compensatory response in mice. (2021)
  • Author(s): Nagai, T., & Kosaki, Y.
  • Organizer: The 81st Annual Meeting of the Japanese Society for Animal Psychology
• [Presentation] Abnormal transition of stimulus representation in ketamine-treated mice: An implication for positive symptoms of schizophrenia. (2021)
  • Author(s): Suzuki, R., & Kosaki, Y.
  • Organizer: The 81st Annual Meeting of the Japanese Society for Animal Psychology
• [Presentation] Biology matters: The role of stimulus modality, duration, and context in the production of different types of CR in Pavlovian fear conditioning in mice. (2021)
  • Author(s): Kosaki, Y., Otsuka, A., & Yamagishi, S.
  • Organizer: The 81st Annual Meeting of the Japanese Society for Animal Psychology
• [Presentation] Effects of pre-exposure to methamphetamine on instrumental conditioning in mice. (2019)
  • Author(s): Nakayama, M., & Kosaki, Y.
  • Organizer: The 79th annual meeting for the Japanase Society of Animal Psychology
• [Presentation] Methamphetamine-induced taste aversion/avoidance in mice. (2019)
  • Author(s): Miki, R., & Kosaki, Y.
  • Organizer: The 79th annual meeting for the Japanase Society of Animal Psychology
• [Presentation] Chronic nicotine administration increases preference for variability in mice. (2019)
  • Author(s): Fuseya, T., Kakimoto, H., Fujimaki, S., & Kosaki, Y.
  • Organizer: The 79th annual meeting for the Japanase Society of Animal Psychology
• [Presentation] Exploring the associative mechanisms underlying instrumental ABA renewal in rats (2019)
  • Author(s): Kosaki, Y. & Fujimaki, S.
  • Organizer: The 79th annual meeting for the Japanase Society of Animal Psychology
• [Presentation] Intranasal oxytocin enhances conditioned social aversion after co-experience of aversive event in mice (2019)
  • Author(s): Murayama, N. & Kosaki, Y.
  • Organizer: The 79th annual meeting for the Japanase Society of Animal Psychology
• [Presentation] Concurrent development of conditioned place preference and odour aversion in compound conditioning with methamphetamine US in mice. (2019)
  • Author(s): Kosaki, Y. & Watanabe, S.
  • Organizer: The 23rd Associative Learning Symposium (Gregynog, Wales)
  • Int'l Joint Research
• [Presentation] Does methamphetamine exposure produce learning under zero contingency? (2018)
  • Author(s): Yutaka Kosaki, Young-Kon Jang, Young-Joo Joh, Risako Miki, Nanami Murayama
  • Organizer: The 78th Annual Meeting of the Japanese Society for Animal Psychology
• [Presentation] マウスにおける薬物条件づけ：メタンフェタミンをUSとした複合条件づけにおける場所選好と匂い嫌悪の並立獲得 (2018)
  • Author(s): 神前裕
  • Organizer: 日本心理学会第82回大会
• [Presentation] メタンフェタミンをUSとした複合条件づけにおいて同時に獲得される場所選好と匂い嫌悪: 薬物依存の心理学的プロセスに対する考察 (2018)
  • Author(s): 神前裕
  • Organizer: 平成30年度 アルコール・薬物依存関連学会合同学術総会
• [Presentation] What we talk about when we talk about conditioning (2018)
  • Author(s): 神前裕
  • Organizer: 第５回印東太郎賞受賞記念講演
  • Invited
• [Funded Workshop] Satellite symposium for the 79th annual JSAP meeting (Guest speaker: Dr. Mark Haselgrove) at Waseda University (2019)
• [Funded Workshop] The 3rd Psychology of Learning Symposium (Guest speaker: Prof. Kennon Andy Lattal), at Waseda University (2019)
• [Funded Workshop] Plenary lecture for the 79th annual meeting for the Japanese Society of Animal Psychology (Dr. Mark Haselgrove) (2019)