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To assess if cocaine's effects on both neuronal and vascular activity contribute to PFC dysfunction, we used optical coherence tomography and multi\u2010wavelength laser speckle to measure vascularization and hemodynamics and used GCaMP6f to monitor intracellular Ca<jats:sup>2+<\/jats:sup>levels ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>in<\/jats:sub>) as a marker of neuronal activity. Rats were given short (1\u00a0hour; ShA) or long (6\u00a0hours; LgA) access cocaine self\u2010administration. As expected, LgA but not ShA rats escalated cocaine intake. In na\u00efve rats, acute cocaine decreased oxygenated hemoglobin, increased deoxygenated hemoglobin and reduced cerebral blood flow in PFC, likely due to cocaine\u2010induced vasoconstriction. ShA rats showed enhanced hemodynamic response and slower recovery after cocaine, versus na\u00efve. LgA rats showed a blunted hemodynamic response, but an enhanced PFC neuronal [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>in<\/jats:sub>increase after cocaine challenge associated with drug intake. Both ShA and LgA groups had higher vessel density, indicative of angiogenesis, presumably to compensate for cocaine's vasoconstricting effects. Cocaine self\u2010administration modified the PFC cerebrovascular responses enhancing it in ShA and attenuating it in LgA animals. In contrast, LgA but not ShA animals showed sensitized neuronal reactivity to acute cocaine in the PFC. The opposite changes in hemodynamics (decreased) and neuronal responses (enhanced) in LgA rats indicate that these constitute distinct effects and suggest that the neuronal and not the vascular effects are associated with escalation of cocaine intake in addiction whereas its vascular effect in PFC might contribute to cognitive deficits that increase vulnerability to relapse.<\/jats:p>","DOI":"10.1111\/adb.12615","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T11:04:46Z","timestamp":1520247886000},"page":"485-497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Enhanced neuronal and blunted hemodynamic reactivity to cocaine in the prefrontal cortex following extended cocaine access: optical imaging study in anesthetized rats"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-3884","authenticated-orcid":false,"given":"Craig P.","family":"Allen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kicheon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora D.","family":"Volkow","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George F.","family":"Koob","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtian","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Ti","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology Rush University Medical Center Chicago Il USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congwu","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5387.298"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130051121"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.12.025"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20829"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03013010"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20037"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.136"},{"key":"e_1_2_6_9_1","volume-title":"2015 National Survey on Drug Use and Health: Detailed Tables","author":"Center for Behavioral Health Statistics and Quality","year":"2016"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12024"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1109\/JSTQE.2015.2503319"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.011417"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06931.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3612-06.2006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","unstructured":"FrangiAF NiessenWJ VinckenKL ViergeverMA(1998)Multiscale vessel enhancement filtering. 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