Study on the neuronal circuit and molecular mechanis underlying decision-making and its application for drug development

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293053
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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(Kenkyū-buntansha): 溝口 博之 名古屋大学, 環境医学研究所, 助教 (70402568)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Taku 名古屋大学, 医学部附属病院, 准教授 (10377426)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経科学 / 脳神経疾患 / 意思決定

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.

Free Research Field

薬理学