{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:13:42Z","timestamp":1778314422175,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Applied Basic Research Program Project of Department of Science and Technology of Liaoning Province","award":["2023JH2\/101600008"],"award-info":[{"award-number":["2023JH2\/101600008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Hypothesis<\/jats:title>\n                    <jats:p>Ketamine triggers cellular pyroptosis through an NOD-like receptor protein 3 (NLRP3)\/caspase-1 pathway, leading to neurotoxicity and cognitive deficits. Dopamine receptor D1 (DRD1) activation, however, suppresses NLRP3 inflammasome activation, thereby curbing inflammation. We hypothesized that ketamine induces pyroptosis through the NLRP3\/caspase-1 pathway, resulting in neurotoxicity and cognitive dysfunction, and that DRD1 activation could counteract these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>To investigate the relationship between DRD1 and ketamine-induced pyroptosis and behavioral changes in mice, we conducted both in vivo and in vitro experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Results<\/jats:title>\n                    <jats:p>Our findings reveal that ketamine induces dose-dependent pyroptosis in HT22 cells, which is alleviated by NLRP3 and caspase-1 antagonists. Furthermore, a DRD1 agonist effectively reduces ketamine-induced pyroptosis in these cells. In vivo, DRD1 activation decreases ketamine-induced NLRP3\/caspase-1-dependent neuronal pyroptosis and ameliorates cognitive impairment in mice by inhibiting NLRP3. Conversely, a DRD1 antagonist enhances NLRP3\/caspase-1-mediated pyroptosis, replicating the behavioral deficits seen with ketamine exposure. Moreover, DRD1-specific knockdown in neuronal cells prevents ketamine-induced cognitive dysfunction and reduces pyroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dopamine receptor D1 activation mitigates ketamine-induced cognitive dysfunction in mice by inhibiting NLRP3\/caspase-1-dependent pyroptosis. These findings offer new insights into the psychobehavioral disorders and cytotoxicity associated with ketamine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/schbul\/sbag063","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:48:09Z","timestamp":1775130489000},"source":"Crossref","is-referenced-by-count":0,"title":["Dopamine Receptor D1 Activation Alleviates Repeated Ketamine Exposure-Induced Cognitive Dysfunction in Mice by Inhibiting NLRP3\/Caspase-1-Dependent Pyroptosis"],"prefix":"10.1093","volume":"52","author":[{"given":"Ying","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Forensic Genetics and Biology, School of Forensic Medicine, China Medical University , Shenyang, Liaoning, 110122 ,","place":["P.R. China"]},{"name":"Key Laboratory of Forensic Bio-evidence Sciences , China Medical University, Shenyang, Liaoning Province, 110122 ,","place":["P.R. 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