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Long-lasting changes in glutamate transmission indicate a role for cocaine-induced synaptic plasticity in the reward circuit. Protein kinase M-\u03b6 (PKM\u03b6), a constitutively active isoform of protein kinase C (PKC), plays a critical role in AMPA receptor (AMPAR) trafficking, including that which occurs after drug exposure. There is evidence for a role of PKM\u03b6 in drug reward as constitutive deletion of PKM\u03b6 potentiates cocaine self-administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>As the PFC plays a role in drug reward and PKM\u03b6 deletion disrupts plasticity the in PFC, we sought to investigate the role of PKM\u03b6 within this brain region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using an inducible genetic deletion model to selectively knockdown PKM\u03b6 in the PFC of male and female mice we sought to investigate the role of PFC PKM\u03b6 in cocaine taking and seeking behaviors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We did not see an effect of PFC PKM\u03b6 knockout on cocaine taking during fixed-ratio self-administration nor am effect on motivation for cocaine on a progressive ratio schedule of reinforcement. However, we found that female, but not male mice, with PFC PKM\u03b6 knockout have blunted cue-induced cocaine seeking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In combination previous studies, PKM\u03b6 is not playing a uniform role in cocaine taking, seeking, or motivation across region. Instead, it is likely that PKM\u03b6 may have additional roles in altering glutamatergic transmission that have yet to be delineated. Sex differences in cue-induced reinstatement may be due to these sex and regional specific differences in PKM\u03b6 mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-026-07024-9","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T03:27:14Z","timestamp":1771903634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PKM\u03b6 in the prefrontal cortex alters cocaine cue-induced reinstatement in a sex-specific manner"],"prefix":"10.1007","author":[{"given":"Alyssa R.","family":"Kniffin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A.","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya R.","family":"Peiris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Briand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"7024_CR1","doi-asserted-by":"publisher","first-page":"e12809","DOI":"10.1111\/adb.12809","volume":"25","author":"H Algallal","year":"2020","unstructured":"Algallal H, Allain F, Ndiaye NA, Samaha A-N (2020) Sex differences in cocaine self-administration behaviour under long access versus intermittent access conditions. 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