{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:58:15Z","timestamp":1790794695785,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T00:00:00Z","timestamp":1551225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["ERC\u20102014\u2010STG 638013"],"award-info":[{"award-number":["ERC\u20102014\u2010STG 638013"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["864.14.010"],"award-info":[{"award-number":["864.14.010"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["2015\/06367\/ALW"],"award-info":[{"award-number":["2015\/06367\/ALW"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>\n                    Obsessive\u2010compulsive disorder (OCD) is characterized by obsessive thinking, compulsive behavior and anxiety, and is often accompanied by cognitive deficits. The neuropathology of OCD involves dysregulation of cortical\u2010striatal circuits. Similar to OCD patients, SAPAP3 knockout mice 3 (SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) exhibit compulsive behavior (grooming), anxiety and dysregulated cortical\u2010striatal function. However, it is unknown whether SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    display cognitive deficits and how these different behavioral traits relate to one another. SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and wild\u2010type (WT) littermates were trained in a Pavlovian conditioning task pairing visual cues with the delivery of sucrose solution. After mice learned to discriminate between a reward\u2010predicting conditioned stimulus (CS+) and a non\u2010reward stimulus (CS\u2212), contingencies were reversed (CS+ became CS\u2212 and vice versa). Additionally, we assessed grooming, anxiety and general activity. SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    acquired Pavlovian approach behavior similarly to WT, albeit less vigorously and with a different strategy. However, unlike WT, SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    were unable to adapt their behavior after contingency reversal, exemplified by a lack of re\u2010establishing CS+ approach behavior (sign tracking). Surprisingly, such behavioral inflexibility, decreased vigor, compulsive grooming and anxiety were unrelated. This study shows that SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    are capable of Pavlovian learning, but lack flexibility to adapt associated conditioned approach behavior. Thus, SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    not only display compulsive\u2010like behavior and anxiety, but also cognitive deficits, confirming and extending the validity of SAPAP3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    as a suitable model for the study of OCD. The observation that compulsive\u2010like behavior, anxiety and behavioral inflexibility were unrelated suggests a non\u2010causal relationship between these traits and may be of clinical relevance for the treatment of OCD.\n                  <\/jats:p>","DOI":"10.1111\/gbb.12557","type":"journal-article","created":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T01:03:41Z","timestamp":1548637421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Behavioral flexibility in a mouse model for obsessive\u2010compulsive disorder: Impaired Pavlovian reversal learning in SAPAP3 mutants"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0853-3763","authenticated-orcid":false,"given":"Bastijn J.G.","family":"van den Boom","sequence":"first","affiliation":[{"name":"Netherlands Institute for Neuroscience Royal Netherlands Academy of Arts and Sciences  Amsterdam The 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6540-6894","authenticated-orcid":false,"given":"Ingo","family":"Willuhn","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Neuroscience Royal Netherlands Academy of Arts and Sciences  Amsterdam The Netherlands"},{"name":"Department of Psychiatry, Amsterdam UMC University of Amsterdam  Amsterdam The 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