| Project/Area Number |
26293053
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
溝口 博之 名古屋大学, 環境医学研究所, 助教 (70402568)
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| Co-Investigator(Renkei-kenkyūsha) |
NAGAI Taku 名古屋大学, 医学部附属病院, 准教授 (10377426)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | 神経科学 / 脳神経疾患 / 意思決定 / 薬理学 / 覚せい剤 / メタンフェタミン / 島皮質 / 大脳基底核 / 神経回路 / DREADDシステム |
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| Outline of Final Research Achievements |
Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders have impairments in decision-making, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-dependent rats choose a high-risk/high-reward option more frequently, and assign higher subjective value to high returns, than control rats, suggesting that decision-making is impaired in the drug-dependent animals. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-dependent animals. Pharmacological studies together with in vivo microdialysis showed that GABAergic neurotransmission in INS played a crucial role in decision-making. Moreover, manipulation of INS activation using DREADD technology resulted in alterations to decision-making.
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