{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:16:18Z","timestamp":1789384578632,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,11,18]],"date-time":"2018-11-18T00:00:00Z","timestamp":1542499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NIDA","award":["DA024038"],"award-info":[{"award-number":["DA024038"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phosphatidylinositide 3\u2010kinases (PI3Ks) are intracellular signal transducer enzymes that recruit protein kinase B (aka Akt) to the cell membrane, the subsequent activation of which regulates many cellular functions. PI3K\/Akt activity is up\u2010regulated within mesocorticolimbic structures in animal models of alcoholism, but less is known regarding PI3K\/Akt activity in animal models of cocaine addiction. Given that prefrontal cortex (PFC) is grossly dysregulated in addiction, we studied how cocaine affects protein indices of PFC PI3K\/Akt activity in rat and mouse models and examined the relevance of PI3K activity for cocaine\u2010related learning. Immunoblotting of mouse medial PFC at 3\u00a0weeks withdrawal from a cocaine\u2010sensitization regimen (seven injections of 30\u00a0mg\/kg, intraperitoneal [IP]) revealed increased kinase activity, as did immunoblotting of tissue from the ventral PFC of rats with a history of long\u2010access intravenous cocaine self\u2010administration (0.25\u00a0mg\/0.1\u00a0mL infusion; 10\u00a0days of 6\u00a0h\/d cocaine access). Interestingly, increased Akt phosphorylation was observed in rat ventromedial PFC at both 3\u2010 and 30\u2010day withdrawal only in animals re\u2010exposed to cocaine\u2010associated cues. A conditioned place\u2010preference paradigm in mice and a cue\u2010elicited drug\u2010seeking test in rats were conducted to determine the functional relevance for elevated PI3K activity for addiction\u2010related behavior. In both cases, an intra\u2010PFC infusion of the PI3K inhibitor wortmannin (50\u03bcM) reduced drug\u2010seeking behavior. Taken together, this cross\u2010species, interdisciplinary, study provides convincing evidence that cocaine history produces an enduring increase in PI3K\/Akt\u2010dependent signaling within the more ventral aspect of the PFC that is relevant to behavioral reactivity to drug\u2010associated cues\/contexts. As such, PI3K inhibitors may well serve as an effective strategy for reducing drug cue reactivity and craving in cocaine addiction.<\/jats:p>","DOI":"10.1111\/adb.12696","type":"journal-article","created":{"date-parts":[[2018,11,18]],"date-time":"2018-11-18T23:14:37Z","timestamp":1542582877000},"page":"1216-1226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["PI3K activation within ventromedial prefrontal cortex regulates the expression of drug\u2010seeking in two rodent species"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1078-1077","authenticated-orcid":false,"given":"Karen K.","family":"Szumlinski","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara Santa Barbara California"},{"name":"Department of Molecular Cellular and Developmental Biology and the Neuroscience Research Institute Santa 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