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Translational imaging techniques are needed to monitor the efficacy of strategies to prevent or mitigate neuroinflammation and alleviate ethanol\u2010induced neurotoxicity. Opioid receptor antagonists such as nalmefene are antagonists of the toll\u2010like receptor 4, which may block the proinflammatory signaling cascade induced by ethanol at this specific target. Male adolescent rats received a validated protocol of ethanol injection (i.p, 3 g\/kg daily for two consecutive days followed by two resting days) during 14 days. Positron emission tomography (PET) imaging with the translocator protein 18 kDa (TSPO) radioligand [<jats:sup>18<\/jats:sup>F]DPA\u2010714 was performed at day\u201015. Toxicity induced by repeated binge\u2010like ethanol exposure (71% mortality) was drastically reduced by nalmefene pretreatment (0.4 mg\/kg, 14% mortality). No mortality was observed in animals that received vehicle (control) or nalmefene alone. Compared with control animals (<jats:italic>n<\/jats:italic> = 10), a significant 2.8\u2010fold to 4.6\u2010fold increase in the volume of distribution (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>) of [<jats:sup>18<\/jats:sup>F]DPA\u2010714 was observed among brain regions in animals exposed to ethanol only (<jats:italic>n<\/jats:italic> = 9). Pretreatment with nalmefene significantly alleviated the neuroimmune response to ethanol exposure in all brain regions (1.2\u2010fold to 2.5\u2010fold increase in <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>; <jats:italic>n<\/jats:italic> = 5). Nalmefene alone (<jats:italic>n<\/jats:italic> = 6) did not impact [<jats:sup>18<\/jats:sup>F]DPA\u2010714 <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub> compared with the control group. Nalmefene may protect against the neuroinflammatory response and overall toxicity associated with binge drinking. [<jats:sup>18<\/jats:sup>F]DPA\u2010714 PET imaging can be used to noninvasively address the neuroimmune impact of ethanol exposure and its modulation by pharmacological strategies in vivo, with translational perspectives.<\/jats:p>","DOI":"10.1111\/adb.12962","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T08:00:44Z","timestamp":1600761644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Nalmefene alleviates the neuroimmune response to repeated binge\u2010like ethanol exposure: A TSPO PET imaging study in adolescent rats"],"prefix":"10.1111","volume":"26","author":[{"given":"Nicolas","family":"Tournier","sequence":"first","affiliation":[{"name":"BioMaps Universit\u00e9 Paris\u2010Saclay, CEA, CNRS, Inserm  Orsay France"},{"name":"Institut des sciences du vivant Fr\u00e9d\u00e9ric Joliot, CEA Service Hospitalier Fr\u00e9d\u00e9ric Joliot  Orsay 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