Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 29, Pages E3930-E3939Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1418014112
Keywords
decision-making; methamphetamine; insular cortex; DREADD; motivational value
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [24111518, 25116515, 25460094, 26120713, 26118506, 26118507]
- MEXT
- Ministry of Health, Labour and Welfare of Japan
- Smoking Research Foundation, Japan
- Uehara Memorial Foundation
- Takeda Science Foundation
- Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation
- Grants-in-Aid for Scientific Research [26293046, 25116515, 15H01428, 26118506, 24111518, 26120713, 25460094, 26118507, 25284003, 26640041] Funding Source: KAKEN
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Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, 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)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making.
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