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Furthermore, the neuroimmune system has been implicated in the development of both AUD and PTSD, but the extent of glial involvement in this context remains unclear. A rodent model was developed to address this gap in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a 15\u2010day exposure to the 5% w\/v EtOH low\u2010fat Lieber\u2010DeCarli liquid diet in combination with the stress\u2010enhanced fear learning (SEFL) paradigm to investigate the effects of chronic EtOH consumption on the development of a PTSD\u2010like phenotype. Next, we used a reverse transcription quantitative real\u2010time polymerase chain reaction to quantify mRNA expression of glial cell markers GFAP (astrocytes) and CD68 (microglia) following severe footshock stress in EtOH\u2010withdrawn rats. Finally, we tested the functional contribution of dorsal hippocampal (DH) astrocytes in the development of SEFL in EtOH\u2010dependent rats using astrocyte\u2010specific G<jats:sub>i<\/jats:sub> designer receptors exclusively activated by designer drugs (G<jats:sub>i<\/jats:sub>\u2010DREADD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results demonstrate that chronic EtOH consumption and withdrawal exacerbate future SEFL. Additionally, we found significantly increased GFAP mRNA expression in the dorsal and ventral hippocampus and amygdalar complex following the severe stressor in EtOH\u2010withdrawn animals. Finally, the stimulation of the astroglial G<jats:sub>i<\/jats:sub>\u2010DREADD during EtOH withdrawal prevented the EtOH\u2010induced enhancement of SEFL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, results indicate that prior EtOH dependence and withdrawal combined with a severe stressor potentiate future enhanced fear learning. Furthermore, DH astrocytes significantly contribute to this change in behavior. Overall, these studies provide insight into the comorbidity of AUD and PTSD and the potential neurobiological mechanisms behind increased susceptibility to a PTSD\u2010like phenotype in individuals with AUD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14963","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T09:54:42Z","timestamp":1667987682000},"page":"2177-2190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chronic ethanol consumption exacerbates future stress\u2010enhanced fear learning, an effect mediated by dorsal hippocampal astrocytes"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-3217","authenticated-orcid":false,"given":"Gillian A.","family":"Barkell","sequence":"first","affiliation":[{"name":"Department of Psychology and Neuroscience University of North Carolina at Chapel Hill  Chapel Hill North Carolina 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