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Increasing evidence suggests that the prelimbic cortex (PL) within the medial prefrontal cortex (mPFC), plays an important role in mediating drug addiction. In this study, we trained adult male Sprague\u2013Dawley rats to establish a model of locomotor sensitization (LS). Moreover, optogenetic inhibition of glutamatergic neurons within the PL inhibited the LS of propofol, whereas optogenetic activation of glutamatergic neurons within the PL promoted the LS of propofol. This effect could be blocked by NBQX (a competitive AMPAR antagonist) pretreatment. Subsequently, a microinjection of NBQX (0.25\u20101\u2009\u03bcg\/0.3\u2009\u03bcL\/site) or saline was administered into the bilateral PL to further examine the impact of AMPARs on the LS of propofol. We found that NBQX pretreatment significantly inhibited both the distance and activity in sensitized rats. The expressions of GluA1 and GluA2 subunits of AMPARs, phosphorylated NR1 subunit of NMDARs, D1Rs, phosphorylated ERK and phosphorylated CREB within mPFC were statistically significantly decreased after NBQX pretreatment, whereas, the expressions of total ERK, total CREB and total NR1 subunit remained unchanged. This evidence verifies the instrumental role of AMPARs within the PL in mediating the LS of propofol, and the NMDAR\u2010D1R\/ERK\/CREB signalling pathway may act as a potential mechanism.<\/jats:p>","DOI":"10.1111\/adb.70078","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T15:24:21Z","timestamp":1753716261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AMPA Receptor Within the Prelimbic Cortex Regulates Propofol\u2010Induced Locomotor Sensitization"],"prefix":"10.1111","volume":"30","author":[{"given":"Chi","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou 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