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MCP\u20101 overexpression in the brain is linked to anxiety, higher alcohol intake, neuronal death, and activation of microglia observed in AUD. The neurosteroid [3\u03b1,5\u03b1][3\u2010hydroxypregnan\u201020\u2010one (3\u03b1,5\u03b1\u2010THP) has been reported as an inhibitor of MyD88\u2010dependent TLR activation and MCP\u20101 overexpression in mouse and human macrophages and the brain of alcohol\u2010preferring (P) rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated how 3\u03b1,5\u03b1\u2010THP regulates MCP\u20101 expression at the cellular level in P rat nucleus accumbens (NAc) and central amygdala (CeA). We focused on neurons, microglia, and astrocytes, examining the individual voxel density of MCP\u20101, neuronal marker NeuN, microglial marker IBA1, astrocytic marker GFAP, and their shared voxel density, defined as intersection. Ethanol\u2010na\u00efve male and female P rats were perfused 1\u2009h after IP injections of 15\u2009mg\/kg of 3\u03b1,5\u03b1\u2010THP, or vehicle. The NAc and CeA were imaged using confocal microscopy following double\u2010immunofluorescence staining for MCP\u20101 with NeuN, IBA1, and GFAP, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MCP\u20101 intersected with NeuN predominantly and IBA1\/GFAP negligibly. 3\u03b1,5\u03b1\u2010THP reduced MCP\u20101 expression in NeuN\u2010labeled cells by 38.27\u2009\u00b1\u200928.09% in male and 56.11\u2009\u00b1\u200921.46% in female NAc, also 37.99\u2009\u00b1\u200919.53% in male and 54.96\u2009\u00b1\u200930.58% in female CeA. In females, 3\u03b1,5\u03b1\u2010THP reduced the MCP\u20101 within IBA1 and GFAP\u2010labeled voxels in the NAc and CeA. Conversely, in males, 3\u03b1,5\u03b1\u2010THP did not significantly alter the MCP\u20101 within IBA1 in NAc or with GFAP in the CeA. Furthermore, 3\u03b1,5\u03b1\u2010THP decreased levels of IBA1 in both regions and sexes with no impact on GFAP or NeuN levels. Secondary analysis performed on data normalized to % control values indicated that no significant sex differences were present.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that 3\u03b1,5\u03b1\u2010THP inhibits neuronal MCP\u20101 expression and decreases the proliferation of microglia in P rats. These results increase our understanding of potential mechanisms for 3\u03b1,5\u03b1\u2010THP modulation of ethanol consumption.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15404","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T02:37:05Z","timestamp":1720751825000},"page":"1693-1703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neurosteroid [3\u03b1,5\u03b1]3\u2010hydroxypregnan\u201020\u2010one inhibition of chemokine monocyte chemoattractant protein\u20101 in alcohol\u2010preferring rat brain neurons, microglia, and astroglia"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-5520","authenticated-orcid":false,"given":"Samantha Lucenell","family":"Ch\u00e9ry","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Neuroscience Curriculum University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd K.","family":"O'Buckley","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Boero","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Psychiatry School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Pharmacology School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Balan","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Psychiatry School of Medicine, The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4441-956X","authenticated-orcid":false,"given":"A. 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