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Here, we assessed the effects of acute cocaine (30\u2009mg\/kg, i.p.) on the reactivity of the PFC to VTA stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a genetically encoded calcium indicator (GCaMP6f), we optically imaged the neuronal Ca<jats:sup>2+<\/jats:sup> reactance in medial PFC (mPFC) in response to \u2018tonic\u2010like\u2019 (5\u00a0Hz) and \u2018phasic\u2010like\u2019 (50\u2009Hz) electrical VTA stimulation. The high temporal and spatial resolutions of our optical system allowed us to capture single Ca<jats:sup>2+<\/jats:sup> neuronal transients from individual stimuli with \u2018tonic\u2010like\u2019 stimulation and to visualize single neuronal activation evoked by \u2018phasic\u2010like\u2019 VTA stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u2018Tonic\u2010like\u2019 VTA stimulation induced a rapid increase in mean neuronal Ca<jats:sup>2+<\/jats:sup> in mPFC followed by a plateau and recovery upon termination of stimulation. After cocaine, the mPFC sensitivity to \u2018tonic\u2010like\u2019 VTA stimulation was attenuated, with a 50.4% reduction (<jats:italic>P<\/jats:italic>\u2009=\u20090.03) in the number of Ca<jats:sup>2+<\/jats:sup> transients corresponding to single electrical stimuli but the recovery time was lengthened (4.30\u2009\u00b1\u20090.25\u2009sec to 5.41\u2009\u00b1\u20090.24\u2009sec, <jats:italic>P<\/jats:italic>\u2009=\u20090.03). \u2018Phasic\u2010like\u2019 stimulation evoked a rapid Ca<jats:sup>2+<\/jats:sup> fluorescence increase in mPFC with an immediate decay process, and while cocaine did not affect the peak response (7.17\u2009\u00b1\u20091.07% versus 7.13\u2009\u00b1\u20090.96%, <jats:italic>P<\/jats:italic>\u2009=\u20090.98) it shortened the recovery time to baseline (3.27\u2009\u00b1\u20090.11\u2009sec versus 2.38\u2009\u00b1\u20090.23\u2009sec, <jats:italic>P<\/jats:italic>\u2009=\u20090.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Acute cocaine impairs reactivity of medial prefrontal cortex (mPFC) to ventral tegmental area stimulation, decreasing its sensitivity to \u2018tonic\u2010like\u2019 stimulation and lengthening the recovery time to return to baseline while shortening it for phasic stimulation. These changes in mPFC might contribute to cocaine binging during intoxication.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.15869","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T07:43:16Z","timestamp":1647416596000},"page":"2242-2253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cocaine's effects on the reactivity of the medial prefrontal cortex to ventral tegmental area stimulation: optical imaging study in mice"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-4398","authenticated-orcid":false,"given":"Kicheon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook NY 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8957-4366","authenticated-orcid":false,"given":"Congwu","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook NY 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