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In this study, we developed a VR-based eye movement desensitization and reprocessing extinction training program tailored for mice. We found that this VR treatment during cocaine extinction prevents reinstatement by suppressing the hyperactivation of glutamatergic excitatory neurons in the intermediate layers of the superior colliculus (SCiCaMKII\u03b1) during exposure to environmental cues. Additionally, SCiCaMKII\u03b1 neurons innervate tyrosine hydroxylase-positive neurons in the locus coeruleus (LCTH). Environmental cues trigger stronger phasic activation of LCTH neurons through this SCiCaMKII\u03b1\u2192LCTH projection, leading to increased dopamine release onto the dorsal CA3 (dCA3) region, thereby facilitating reinstatement. Furthermore, we demonstrate that VR treatment effectively inhibits the neural circuitry involving SCiCaMKII\u03b1\u2192LCTH\u2192dCA3 in response to environmental cues, thus preventing cocaine reinstatement. Our findings suggest that VR treatment may represent a promising strategy for achieving drug abstinence.<\/jats:p>","DOI":"10.1093\/nsr\/nwae467","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T01:35:52Z","timestamp":1735263352000},"source":"Crossref","is-referenced-by-count":6,"title":["A superior colliculus-originating circuit prevents cocaine reinstatement via VR-based eye movement desensitization treatment"],"prefix":"10.1093","volume":"12","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and 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