title: Insular neural system controls decision-making in healthy and methamphetamine-treated rats.
abstract: 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.
authors.affiliation: Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.affiliation: Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Kentaro
authors.initials: K
authors.lastname: Katahira
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Ayumu
authors.initials: A
authors.lastname: Inutsuka
authors.affiliation: Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukumoto
authors.affiliation: Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.affiliation: Department of Brain Functions, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.affiliation: Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohira
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; kyamada@med.nagoya-u.ac.jp.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000502:physiology*; D002755:Choice Behavior; D003657:Decision Making; D005715:Gambling; D008297:Male; D018782:Maze Learning; D008694:Methamphetamine / Q000008:administration & dosage*; D009042:Motivation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012201:Reward; D012309:Risk-Taking; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid
keywords: DREADD; decision-making; insular cortex; methamphetamine; motivational value