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However, both pre-clinical and clinical studies of these co-occurring disorders have disproportionately represented male subjects, limiting the applicability of these findings. Our previous work has identified chronic escalating heroin administration and withdrawal can produce enhanced fear learning. This behavior is associated with an increase in dorsal hippocampal (DH) interleukin-1\u03b2 (IL-1\u03b2), tumor necrosis factor-\u03b1 (TNF-\u03b1), and glial fibrillary acidic protein (GFAP) immunoreactivity. Further, we have shown that these increases in IL-1\u03b2 and TNF-\u03b1 are mechanistically necessary for the development of enhanced fear learning. Although these are exciting findings, this paradigm has only been studied in males. The current studies aim to examine sex differences in the behavioral and neuroimmune effects of chronic heroin withdrawal and future enhanced fear learning. In turn, we determined that chronic escalating heroin administration can produce withdrawal in female rats comparable to male rats. Subsequently, we examined the consequence of heroin withdrawal on future enhanced fear learning and IL-1\u03b2, TNF-\u03b1, and GFAP immunoreactivity. Strikingly, we identified sex differences in these neuroimmune measures, as chronic heroin administration and withdrawal does not produce enhanced fear learning or immunoreactivity changes in females. Moreover, we determined whether heroin withdrawal produces short-term and long-term anxiety behaviors in both female and males. Collectively, these novel experiments are the first to test whether heroin withdrawal can sensitize future fear learning, produce neurobiological changes, and cause short-term and long-term anxiety behaviors in female rats.<\/jats:p>","DOI":"10.1007\/s00213-023-06310-0","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T05:02:57Z","timestamp":1673499777000},"page":"347-359","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sex-differences in anxiety, neuroinflammatory markers, and enhanced fear learning following chronic heroin withdrawal"],"prefix":"10.1007","volume":"240","author":[{"given":"Shveta V.","family":"Parekh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia O.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian A.","family":"Barkell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-7910","authenticated-orcid":false,"given":"Donald T.","family":"Lysle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"issue":"1","key":"6310_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13293-020-00303-w","volume":"11","author":"L Albrechet-Souza","year":"2020","unstructured":"Albrechet-Souza L, Schratz CL, Gilpin NW (2020) Sex differences in traumatic stress reactivity in rats with and without a history of alcohol drinking. 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