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However, whether phospholyration of Akt (p\u2010Akt) mediates heroin relapse remains unclear. Here, we aimed to explore the role of p\u2010Akt in the nucleus accumbens (NAc) in cue\u2010induced heroin\u2010seeking behaviors after withdrawal. First, rats were trained to self\u2010administer heroin for 14\u00a0days, after which we assessed heroin\u2010seeking behaviors induced by a context cue (CC) or by discrete conditioned cues (CS) after 1\u00a0day or 14\u00a0days of withdrawal. We found that the active responses induced by CC or CS after 14\u00a0days of withdrawal were higher than those after 1\u00a0day of withdrawal. Meanwhile, the expression of p\u2010Akt in the NAc was also greatest when rats were exposed to the CS after 14\u00a0days of withdrawal. Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS\u2010induced heroin\u2010seeking behaviors after 14\u00a0days of withdrawal, paralleling the decreased levels of p\u2010Akt in the NAc. Finally, Akt1 or \u03b2\u2010arrestin 2 was downregulated via a lentiviral injection to assess the effect on heroin seeking after 14\u00a0days of withdrawal. CS\u2010induced heroin\u2010seeking behavior was inhibited by downregulation of Akt1, but not \u03b2\u2010arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin\u2010seeking behavior, suggesting that the PI3K\/Akt pathways may be involved in the process of heroin relapse and addiction.<\/jats:p>","DOI":"10.1111\/adb.13013","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T05:05:45Z","timestamp":1614056745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Akt and its phosphorylation in nucleus accumbens mediate heroin\u2010seeking behavior induced by cues in rats"],"prefix":"10.1111","volume":"26","author":[{"given":"Huaqiang","family":"Zhu","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Addiction Research, Ningbo Kangning Hospital, School of Medicine Ningbo University  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School of Medicine Ningbo University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxiao","family":"Hong","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Addiction Research, Ningbo Kangning Hospital, School of Medicine Ningbo University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifen","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Addiction Research, Ningbo Kangning Hospital, School of Medicine Ningbo University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4804-7559","authenticated-orcid":false,"given":"Wenhua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Addiction Research, Ningbo Kangning Hospital, School of Medicine Ningbo University  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