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Parvalbumin (PV)\u2010containing GABAergic interneurons powerfully control the output of the mPFC, yet few studies have focused on how these neurons modulate cocaine\u2010seeking behaviour. Most PV neurons are surrounded by perineuronal nets (PNNs), which regulate the firing of PV neurons. We examined staining intensity and number of PV and PNNs after long\u2010access (6\u00a0h\/day) cocaine self\u2010administration in rats followed by either 8\u201310\u00a0days extinction\u2009\u00b1\u2009cue\u2010induced reinstatement or short\u2010term (1\u20132\u00a0days) or long\u2010term (30\u201331\u2009days) abstinence\u2009\u00b1\u2009cue\u2010induced reinstatement. The intensity of PNNs was increased in the prelimbic and infralimbic PFC after long\u2010term abstinence in the absence of cue reinstatement and after cue reinstatement following both daily extinction sessions and after a 30\u2010day abstinence period. PV intensity was increased after 30\u2009days of abstinence in the prelimbic but not infralimbic PFC. Enzymatic removal of PNNs with chondroitinase ABC (ABC) in the prelimbic PFC did not prevent incubation of cue\u2010induced reinstatement but decreased cocaine\u2010seeking behaviour at both 2 and 31\u2009days of abstinence, and this decrease at 31\u2009days was accompanied by reduced c\u2010Fos levels in the prelimbic PFC. Increases in PNN intensity have generally been associated with the loss of plasticity, suggesting that the persistent and chronic nature of cocaine use disorder may in part be attributed to long\u2010lasting increases in PNN intensity that reduce the ability of stimuli to alter synaptic input to underlying PV neurons.<\/jats:p>","DOI":"10.1111\/adb.13334","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T17:33:53Z","timestamp":1696268033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Enhanced expression of parvalbumin and perineuronal nets in the medial prefrontal cortex after extended\u2010access cocaine self\u2010administration in rats"],"prefix":"10.1111","volume":"28","author":[{"given":"Jereme C.","family":"Wingert","sequence":"first","affiliation":[{"name":"Neuroscience Washington State University  Vancouver Washington USA"},{"name":"R.S. 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