{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:01:50Z","timestamp":1779192110135,"version":"3.51.4"},"reference-count":61,"publisher":"Society for Neuroscience","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japanese Society for the Promotion of Science","doi-asserted-by":"crossref","award":["16H05091"],"award-info":[{"award-number":["16H05091"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18ak0101088h0001"],"award-info":[{"award-number":["18ak0101088h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by the repeated rise of concerns (obsessions) and repetitive unwanted behavior (compulsions). Although selective serotonin reuptake inhibitors (SSRIs) is the first-choice drug, response rates to SSRI treatment vary between symptom dimensions. In this study, to find a therapeutic target for SSRI-resilient OCD symptoms, we evaluated treatment responses of quinpirole (QNP) sensitization-induced OCD-related behaviors in mice. SSRI administration rescued the cognitive inflexibility, as well as hyperactivity in the lateral orbitofrontal cortex (lOFC), while no improvement was observed for the repetitive behavior. D<jats:sub>2<\/jats:sub>receptor signaling in the central striatum (CS) was involved in SSRI-resistant repetitive behavior. An adenosine A<jats:sub>2A<\/jats:sub>antagonist, istradefylline, which rescued abnormal excitatory synaptic function in the CS indirect pathway medium spiny neurons (MSNs) of sensitized mice, alleviated both of the QNP-induced abnormal behaviors with only short-term administration. These results provide a new insight into therapeutic strategies for SSRI-resistant OCD symptoms and indicate the potential of A<jats:sub>2A<\/jats:sub>antagonists as a rapid-acting anti-OCD drug.<\/jats:p>","DOI":"10.1523\/eneuro.0366-18.2019","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T22:55:14Z","timestamp":1550616914000},"page":"ENEURO.0366-18.2019","source":"Crossref","is-referenced-by-count":18,"title":["An Adenosine A<sub>2A<\/sub>Receptor Antagonist Improves Multiple Symptoms of Repeated Quinpirole-Induced Psychosis"],"prefix":"10.1523","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4854-2100","authenticated-orcid":false,"given":"Nozomi","family":"Asaoka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Nishitani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruko","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuma","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hikari","family":"Hatakama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-732X","authenticated-orcid":false,"given":"Kazuki","family":"Nagayasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-0978","authenticated-orcid":false,"given":"Hisashi","family":"Shirakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-0843","authenticated-orcid":false,"given":"Takayuki","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5152-5809","authenticated-orcid":false,"given":"Shuji","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1234733"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.2","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S62785"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13599-3"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3639-07.2008"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.5","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(94)90011-6"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.6","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1987.01800150017003"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.7","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.173"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.8","doi-asserted-by":"publisher","DOI":"10.1177\/0897190014521996"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.01.022"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2008.07.016"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-20-08911.2002"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232380"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.13","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3743"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.14","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852913000564"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.4.1970"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.07.002"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.05.012"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.18","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.95"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.19","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10071062"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11305"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.21","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4275"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00113-6"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3264"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.04.043"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.25","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00151"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.26","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2013.87"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.27","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19103"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.08.031"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.29","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1456"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2009.06.010"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.04.040"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.32","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.227"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.11.003"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2006.12.018"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.07.041"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(99)00059-4"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.07.030"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.38","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.39","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291709005297"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.12.032"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.41","first-page":"6","article-title":"A qualitative analysis of nonresponse: management of treatment-refractory obsessive-compulsive disorder","volume":"65","year":"2004","journal-title":"J Clin Psychiatry"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.42","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3746"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706929105"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02615-9"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.45","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00082-2"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.02.027"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.47","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12971"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.48","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160575"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.49","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.200"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216264109"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.51","doi-asserted-by":"publisher","DOI":"10.1080\/00048670802203442"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.52","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00209"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.53","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244757"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.54","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.112.6.1475"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.55","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00683.2005"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cogbrainres.2005.01.004"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.57","doi-asserted-by":"publisher","DOI":"10.1002\/da.22259"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.58","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70287-X"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.59","doi-asserted-by":"publisher","DOI":"10.1038\/nature06104"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.60","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4215-09.2009"},{"key":"2023041302132335000_6.1.ENEURO.0366-18.2019.61","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701736114"}],"container-title":["eneuro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0366-18.2019","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0366-18.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T09:42:18Z","timestamp":1681378938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eneuro.org\/lookup\/doi\/10.1523\/ENEURO.0366-18.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,2,28]]},"published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1523\/ENEURO.0366-18.2019"],"URL":"https:\/\/doi.org\/10.1523\/eneuro.0366-18.2019","relation":{},"ISSN":["2373-2822"],"issn-type":[{"value":"2373-2822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1]]}}}