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Such alterations are hypothesized to underlie enduring maladaptive behaviours observed in cocaine use disorder (CUD). The current study explored whether synaptic density is altered in CUD. Fifteen individuals with DSM\u20105 CUD and 15 demographically matched healthy control (HC) subjects participated in a single\n                    <jats:sup>11<\/jats:sup>\n                    C\u2010UCB\u2010J positron emission tomography scan to assess density of synaptic vesicle glycoprotein 2A (SV2A). The volume of distribution (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    ) and the plasma\u2010free fraction\u2010corrected form of the total volume of distribution (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    <jats:italic>\/f<\/jats:italic>\n                    <jats:sub>P<\/jats:sub>\n                    ) were analysed in the anterior cingulate cortex (ACC), dorsomedial and ventromedial prefrontal cortex (PFC), lateral and medial orbitofrontal cortex (OFC) and ventral striatum. A significant diagnostic\u2010group\u2010by\u2010region interaction was observed for\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    and\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    <jats:italic>\/f<\/jats:italic>\n                    <jats:sub>P<\/jats:sub>\n                    . Post hoc analyses revealed no differences on\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    , while for\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    \/\n                    <jats:italic>f<\/jats:italic>\n                    <jats:sub>P<\/jats:sub>\n                    showed lower values in CUD as compared with HC subjects in the ACC (\u221210.9%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02), ventromedial PFC (\u22129.9%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) and medial OFC (\u22129.9%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). Regional\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    \/\n                    <jats:italic>f<\/jats:italic>\n                    <jats:sub>P<\/jats:sub>\n                    values in CUD, though unrelated to measures of lifetime cocaine use, were positively correlated with the frequency of recent cocaine use (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02\u20130.03) and negatively correlated with cocaine abstinence (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008\u20130.03). These findings provide initial preliminary in vivo evidence of altered (lower) synaptic density in the PFC of humans with CUD. Cross\u2010sectional variation in SV2A availability as a function of recent cocaine use and abstinence suggests that synaptic density may be dynamically and plastically regulated by acute cocaine, an observation that merits direct testing by studies using more definitive longitudinal designs.\n                  <\/jats:p>","DOI":"10.1111\/adb.13123","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T19:26:42Z","timestamp":1638386802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory\n                    <sup>11<\/sup>\n                    C\u2010UCB\u2010J positron emission tomography study in humans"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-9878","authenticated-orcid":false,"given":"Gustavo 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