{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:29:19Z","timestamp":1790699359554,"version":"4.1.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,7,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Patients with addiction have a greater tendency to engage in risk-taking behavior. However, the neural substrates responsible for these deficits remain unknown. Here we demonstrated that chronic methamphetamine-treated rats preferred high-risk\/high-reward actions and assigned higher value to high returns, indicative of altered decision-making. Pharmacological studies revealed that the insular neural system controls decision-making in both healthy and methamphetamine-treated rats. We further confirmed the role of the insular cortex in decision-making using designer receptor exclusively activated by designer drug technology. Because decision-making is a cognitive process that influences many aspects of daily living and both mental and physical health, the findings of this study have broader implications.<\/jats:p>","DOI":"10.1073\/pnas.1418014112","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T23:00:04Z","timestamp":1436223604000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["Insular neural system controls decision-making in healthy and methamphetamine-treated rats"],"prefix":"10.1073","volume":"112","author":[{"given":"Hiroyuki","family":"Mizoguchi","sequence":"first","affiliation":[{"name":"Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Katahira","sequence":"additional","affiliation":[{"name":"Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumu","family":"Inutsuka","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;"},{"name":"Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sato","sequence":"additional","affiliation":[{"name":"Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Brain Functions, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ohira","sequence":"additional","affiliation":[{"name":"Department of Psychology, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyofumi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,7,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.06.004"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.148"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.04.008"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.187.3.209"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.12091257"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-0277(94)90018-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.8.1403"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5587-09.2010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.08.011"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.09.007"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1142997"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-1871-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3772-11.2011"},{"key":"e_1_3_3_14_2","unstructured":"ND Daw Trial-by-trial data analysis using computational models. Decision Making Affect and Learning: Attention and Performance XXIII (Oxford University Press Oxford) pp 1\u201326. (2009)."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.02.029"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-010-0268-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2278-12.2012"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3932(03)00039-3"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn066"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9280.2005.01646.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3758\/BF03196629"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2489-13.2014"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321596111"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1554-07.2007"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12475"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3281532bd7"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","unstructured":"MR Mitchell Adolescent risk taking cocaine self-administration and striatal dopamine signaling. Neuropsychopharmacology 39(4):955\u2013962. (2014).","DOI":"10.1038\/npp.2013.295"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1278-13.2013"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.09.009"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.12.024"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00225-2"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-21-07931.2003"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.7.761"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300115"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00576.x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1238"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4692-12.2013"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-062111-150512"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1261-1"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.41"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.03.038"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8232-6"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.7"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0353-z"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2005.11.030"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.07.015"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmp.2015.03.006"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2011.00311"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3118-11.2011"},{"key":"e_1_3_3_50_2","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos G","year":"2007","unstructured":"G Paxinos, C Watson The Rat Brain in Stereotaxic Coordinates (Academic, 6th Ed, Amsterdam, 2007).","edition":"6"},{"key":"e_1_3_3_51_2","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/j.1471-4159.2006.04288.x","article-title":"Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice","volume":"100","author":"Mizoguchi H","year":"2007","unstructured":"H Mizoguchi, , Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice. J Neurochem 100, 1579\u20131588 (2007).","journal-title":"J Neurochem"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6730-10.2011"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.04.006"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214985"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1418014112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T21:59:16Z","timestamp":1748469556000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1418014112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,6]]},"references-count":54,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2015,7,21]]}},"alternative-id":["10.1073\/pnas.1418014112"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1418014112","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,6]]},"assertion":[{"value":"2015-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}