{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:16:58Z","timestamp":1753877818479,"version":"3.41.2"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA027544"],"award-info":[{"award-number":["AA027544"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA048742","DA034696","DA007234"],"award-info":[{"award-number":["DA048742","DA034696","DA007234"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug\u2010induced neuroadaptations in the prefrontal cortex (PFC) have been implicated in drug\u2010associated memories that motivate continued drug use. Chronic cocaine exposure increases pyramidal neuron excitability in the prelimbic subregion of the PFC (PL), an adaptation that has been attributed in part to a suppression of inhibitory signalling mediated by the GABA<jats:sub>B<\/jats:sub> receptor (GABA<jats:sub>B<\/jats:sub>R) and G protein\u2010gated inwardly rectifying K<jats:sup>+<\/jats:sup> (GIRK\/Kir3) channels. Although reduced GIRK channel activity in PL pyramidal neurons enhances the motor\u2010stimulatory effect of cocaine in mice, the impact on cocaine reward and associated memories remains unclear. Here, we employed Cre\u2010 and CRISPR\/Cas9\u2010based viral manipulation strategies to evaluate the impact of GIRK channel or GABA<jats:sub>B<\/jats:sub>R ablation in PL pyramidal neurons on cocaine\u2010induced conditioned place preference (CPP) and extinction. Neither ablation of GIRK channels nor GABA<jats:sub>B<\/jats:sub>R impacted the acquisition of cocaine CPP. GIRK channel ablation in PL pyramidal neurons, however, impaired extinction of cocaine CPP in male but not female mice. Since ablation of GIRK channels but not GABA<jats:sub>B<\/jats:sub>R increased PL pyramidal neuron excitability, we used a chemogenetic approach to determine if acute excitation of PL pyramidal neurons impaired the expression of extinction in male mice. While acute chemogenetic excitation of PL pyramidal neurons induced locomotor hyperactivity, it did not impair the extinction of cocaine CPP. Lastly, we found that persistent enhancement of GIRK channel activity in PL pyramidal neurons accelerated the extinction of cocaine CPP. Collectively, our findings show that the strength of GIRK channel activity in PL pyramidal neurons bi\u2010directionally regulates cocaine CPP extinction in male mice.<\/jats:p>","DOI":"10.1111\/adb.13256","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T12:32:51Z","timestamp":1669293171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GIRK channel activity in prelimbic pyramidal neurons regulates the extinction of cocaine conditioned place preference in male mice"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1473-1739","authenticated-orcid":false,"given":"Timothy R.","family":"Rose","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota 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