{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:02:29Z","timestamp":1784595749465,"version":"3.55.0"},"reference-count":67,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3300905"],"award-info":[{"award-number":["2022YFC3300905"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471516"],"award-info":[{"award-number":["82471516"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    4F\u2010ABUTINACA, a fourth\u2010generation synthetic cannabinoid, has been identified in branded herbal smoking mixtures and e\u2010cigarettes seized in China. However, its potential for abuse and its corresponding neurotoxic effects remain poorly understood. In the present study, we evaluated the abuse potential of 4F\u2010ABUTINACA using the intravenous self\u2010administration (IVSA) model and assessed anxiety\u2010like behaviour using the open\u2010field test (OFT) and the elevated plus maze test (EPM). Additionally, neuronal injury, apoptosis, alterations in glia expression and the BDNF\u2010TrkB\u2010AKT signalling pathway in multiple brain regions were assessed simultaneously. Rats acquired stable nose\u2010poke operant response for self\u2010administering 4F\u2010ABUTINACA (0.00625\u2009mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7infusion\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and showed significant drug\u2010seeking behaviour induced by conditioned cues. Persistent anxiety\u2010like behaviours were observed both immediately after drug\u2010taking (SA group) and cue\u2010induced reinstatement testing after a 14\u2010day extinction period (CIR group). Histochemical analysis revealed more pronounced neuronal injury and apoptosis in the hippocampus, prefrontal cortex (PFC) and nucleus accumbens (NAc) in the SA group than in the CIR group. Reactive astrogliosis and microgliosis were observed in the hippocampus and the PFC in the SA group, whereas the numbers of microglia and astrocytes decreased in the NAc of the CIR group. We also found the distinct region\u2010specific alterations in the BDNF\u2010TrkB\u2010AKT signalling pathway expression profile between the SA and CIR groups. The present results demonstrate that 4F\u2010ABUTINACA exhibits significant potential for abuse and produces anxiety\u2010like behaviour during both the active drug\u2010taking and cue\u2010induced relapse stages, which are associated with the neuropathological alterations in specific brain regions.\n                  <\/jats:p>","DOI":"10.1111\/adb.70177","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:49:43Z","timestamp":1783046983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abuse Potential and Neurotoxic Effects of the Synthetic Cannabinoid 4F\u2010ABUTINACA Self\u2010Administration in Adult Male Rats"],"prefix":"10.1111","volume":"31","author":[{"given":"Baobao","family":"Shi","sequence":"first","affiliation":[{"name":"School of Psychology and Mental Health North China University of Science and Technology  Tangshan Hebei Province 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Health  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Affiliated Kangning Hospital of Ningbo University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Affiliated Kangning Hospital of Ningbo University  Ningbo Zhejiang China"},{"name":"Zhejiang Key Laboratory of Drug Addiction and Brain Health  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[{"name":"Office of China National Narcotics Control Commission China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control  Beijing 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