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Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine\u2010addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine\u2010associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine\u2010induced conditioned place preference (CPP) paradigm. We suppressed mPFC neuronal activity in a cell\u2010type\u2013 and timing\u2010dependent manner. C57BL\/6J wild\u2010type mice received bilateral intra\u2010mPFC infusion of an adeno\u2010associated virus (AAV) expressing inhibitory DREADD (hM4Di) under the control of CaMKII promotor to selectively suppress mPFC pyramidal neurons. <jats:italic>GAD67\u2010Cre<\/jats:italic> mice received bilateral intra\u2010mPFC infusion of a <jats:italic>Cre<\/jats:italic>\u2010dependent AAV expressing hM4Di to specifically silence GABAergic neurons. Chemogenetic suppression of mPFC pyramidal neurons significantly attenuated both the acquisition and expression of cocaine CPP, while suppression of mPFC GABAergic neurons affected neither the acquisition nor expression of cocaine CPP. Moreover, chemogenetic inhibition of mPFC glutamatergic neurons did not affect the acquisition and expression of lithium chloride\u2010induced conditioned place aversion. These results suggest that the activation of glutamatergic, but not GABAergic, neurons in the mPFC mediates both the formation and retrieval of cocaine\u2010associated memories.<\/jats:p>","DOI":"10.1111\/adb.12723","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T05:18:51Z","timestamp":1549603131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine\u2010associated memories in mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Tong","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Yanagida","sequence":"additional","affiliation":[{"name":"Laboratory of 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