Effect of drugs of abuse on reward-based decision-making in rodents

• Project/Area Number: 23659135
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Nagoya University
• Principal Investigator: YAMADA Kiyofumi 名古屋大学, 医学部附属病院, 教授 (30303639)
• Co-Investigator(Renkei-kenkyūsha): MIZOGUCHI Hiroyuki 名古屋大学, 環境医学研究所, 助教 (70402568)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 覚せい剤 / 薬物依存症 / ギャンブルテスト / 意思決定 / メタンフェタミン / 薬物依存 / 動物モデル

Research Abstract

In the present study, we developed a gambling testfor rodents using a radial-arm maze to address the issue of decision-making in patients with drug dependence. Rats were trained in the cost/benefit decision-making task, in which they chose one of four arms [one low risk/low return (LL) arm, one high risk/high return (HH) arm and two empty arms]. The test consisted of consecutive 16 trials a day. Following extensive testing, naive rats showed the choice behavior, which is dependent on reward probability and reward value of the arms. Following chronic treatment with methamphetamine, the animals chose HH arms more frequently than did saline-treated control rats. After the gambling test, c-Fos expression was markedly increased in the insular cortex, striatum, and nucleus accumbens of methamphetamine-dependent rats compared to saline-treated control rats. Our findings suggest that chronic methamphetamine treatment may lead to alternations of reward-based decision-making. Aberrant activation of the cortico-striatal pathway from insular cortex to striatum may be associated with the impairment of reward-based decision-making in methamphetamine-dependent rats.

Research Products

• [Journal Article] Neuronal PAS domain domain protein 4 (Npas4) regulates neurite outgrowth and phosphorylation of synapsin I. (2013)
  • Author(s): Yun J, Nagai T, Furukawa-Hibi Y, Kuroda K, Kaibuchi K, Greenberg ME, and Yamada K
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 4 Pages: 2655-2664
  • DOI: 10.1074/jbc.m112.413310
  • Peer Reviewed
• [Journal Article] Repeated treatment with nicotine induces phosphorylation of NMDA receptor NR2B subunit in the brain regions involved in behavioral sensitization. (2012)
  • Author(s): Nakajima A, Kinugasa Y, Torii J, Hishinuma T, Tomioka Y, Yamada K and Yamakuni T
  • Journal Title: Neurosci. Lett Volume: 524 Issue: 2 Pages: 133-138
  • DOI: 10.1016/j.neulet.2012.07.022
  • Peer Reviewed
• [Journal Article] D-Serine Ameliorates Neonatal PolyI:C Treatment–Induced Emotional and Cognitive Impairments in Adult Mice (2012)
  • Author(s): Nagai T, Yu J, Kitahara Y, Nabeshima T and Yamada K
  • Journal Title: Journal of Pharmacological Sciences Volume: 120 Issue: 3 Pages: 213-227
  • DOI: 10.1254/jphs.12142FP
  • NAID: 10031147568
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] Butrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-βpeptide in mice (2011)
  • Author(s): Yoko Furukawa-Hibi, et al
  • Journal Title: Behavioural Brain Research Volume: 225 Issue: 1 Pages: 222-229
  • DOI: 10.1016/j.bbr.2011.07.035
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus (2011)
  • Author(s): H Mizoguchi, J Nakade, M Tachibana, D Ibi, E Someya, H Koike, H Kamei, T Nabeshima, S Itohara, K Takuma, M Sawada, J Sato, K Yamada
  • Journal Title: Journal of Neuroscience Volume: 31 Issue: 36 Pages: 12963-12971
  • DOI: 10.1523/jneurosci.3118-11.2011
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinases contribute to neuronal dysfunction in animal models of drug dependence, Alzheimer’s disease, and epilepsy. (2011)
  • Author(s): Mizoguchi H, Yamada K and Nabeshima T
  • Journal Title: Biochem. Res. Int. Volume: 2011 Pages: 681385-681385
  • DOI: 10.1155/2011/681385
  • Peer Reviewed
• [Presentation] (2012)
  • Author(s): 溝口博之、山田清文
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋 名古屋国際会議場
• [Presentation] (2012)
  • Author(s): Mizoguchi H, Yamada K
  • Organizer: 2012 ISBRA World congress
  • Place of Presentation: 札幌 札幌コンベンションセンター
• [Presentation] (2012)
  • Author(s): 山田清文、溝口博之
  • Organizer: 平成 24 年度アルコール・薬物依存関連学会合同学術総会
  • Place of Presentation: 札幌 札幌コンベンションセンター
• [Presentation] 報酬に基づく意思決定機構に対する覚せい剤の効果
  • Author(s): 溝口博之、佐藤純、山田清文
  • Organizer: 平成23年度アルコール・薬物依存関連学会合同学術総会
  • Place of Presentation: 名古屋、愛知県産業労働センター
• [Presentation] 内因性薬物依存修飾因子
  • Author(s): 山田清文
  • Organizer: 第38回日本トキシコロジー学会学術年会
  • Place of Presentation: 横浜、パシフィコ横浜
• [Presentation] Neuronal mechanisms of methamphetamine-seeking behavior in mice
  • Author(s): Yamada K, Yan Y, Nitta A, Mizoguchi H, Nabeshima T
  • Organizer: 5th CINP Pacific-Asia Regional Meeting 2011
  • Place of Presentation: Kuala Lumpur, Malaysia
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/pharmacy/02/index.html