{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:30:14Z","timestamp":1777984214261,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["22\u201006943S"],"award-info":[{"award-number":["22\u201006943S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Social withdrawal is a core negative symptom of schizophrenia and remains poorly understood at the molecular level. Dysregulation of the endocannabinoid system has been implicated in social behavior, yet its downstream signaling mechanisms are not fully characterized. In this context, this study examined the effects of the fatty acid amide hydrolase (FAAH) inhibitor, URB597, on CREB expression and its phosphorylation at serine 133 (pCREB) in saline\u2010treated (1\u2009mL\/kg, i.p.) or phencyclidine\u2010treated (PCP; 5\u2009mg\/kg, i.p., twice a day for 7\u2009days) rats engaged in social interaction. CREB and pCREB expression was measured in six cortical regions selected for their established roles in social behavior: the prelimbic cortex (A32V), the cingulate cortex (A32D), the ventral orbital cortex (VO), the lateral orbital cortex (LO), the agranular insular cortex (AI), and the infralimbic cortex (A25). PCP\u2010treated rats showed reduced social interaction, and URB597 reversed this deficit, whereas the same treatment decreased social interaction in saline controls. Across the six prefrontal and insular regions, CREB expression was largely unchanged, apart from a URB597\u2010related reduction in the LO (main effect,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) and an increase in the AI of PCP\u2010treated rats. URB597 also reduced pCREB in VO (main effect,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In contrast, the AI showed clear group\u2010specific effects: Both PCP\u2010treated rats receiving vehicle and saline\u2010treated rats receiving URB597 exhibited reduced pCREB relative to saline controls. Although URB597 did not significantly reverse the pCREB reduction in PCP\u2010treated rats, pCREB levels in the AI positively correlated with time spent in social interaction (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.43,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). These findings identify the AI as a key neural substrate underlying social withdrawal in this model and suggest that targeting the endocannabinoid system within this region may represent a promising therapeutic strategy for alleviating the negative symptoms of schizophrenia.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70427","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T08:21:25Z","timestamp":1770798085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Fatty Acid Amide Hydrolase Alters Cortical CREB Signaling and Social Behavior in a Rat Model of Schizophrenia"],"prefix":"10.1111","volume":"63","author":[{"given":"Aditya","family":"Kumar","sequence":"first","affiliation":[{"name":"Schizophrenia Models for Advancing Research and Treatment, Preclinical Research Program National Institute of Mental Health  Prague East Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenka","family":"Seillier","sequence":"additional","affiliation":[{"name":"Department of Physiology, Third Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kucha\u0159","sequence":"additional","affiliation":[{"name":"Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds University of Chemistry and Technology Prague  Prague Czech Republic"},{"name":"Psychedelic Research Center National Institute of Mental Health  Prague East Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-2561","authenticated-orcid":false,"given":"Alexandre","family":"Seillier","sequence":"additional","affiliation":[{"name":"Schizophrenia Models for Advancing Research and Treatment, Preclinical Research Program National Institute of Mental Health  Prague East Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500587102"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22272"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22213"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2015.01805"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan8868"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167\u20109473(99)00057\u20102"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbab137"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.026"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.020"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2017.03.005"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","unstructured":"Espinosa P. 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