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S-Equol (SE), a selective estrogen receptor \u03b2 agonist, has been implicated as a neuroprotective and\/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for motivational alterations, however, has yet to be systematically evaluated. Thus, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2\u00a0mg) or vehicle and assessed in a series of tasks to evaluate goal-directed and drug-seeking behavior. First, at the genotypic level, motivational deficits in HIV-1 Tg rats treated with vehicle were characterized by a\n                    <jats:italic>diminished<\/jats:italic>\n                    reinforcing efficacy of, and sensitivity to, sucrose. Motivational dysregulation was evidenced by\n                    <jats:italic>enhanced<\/jats:italic>\n                    drug-seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated both motivational deficits and dysregulation in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited lower levels of dendritic branching and a shift towards longer dendritic spines with decreased head diameter. Treatment with SE, however, led to long-term enhancements in dendritic spine morphology in HIV-1 Tg animals supporting a potential underlying basis by which SE exerts its therapeutic effects. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-91240-0","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T06:04:47Z","timestamp":1622786687000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["S-Equol mitigates motivational deficits and dysregulation associated with HIV-1"],"prefix":"10.1038","volume":"11","author":[{"given":"Kristen A.","family":"McLaurin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Bertrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Illenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Harrod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Mactutus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie M.","family":"Booze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"91240_CR1","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/npp.2017.228","volume":"43","author":"RA Wise","year":"2018","unstructured":"Wise, R. 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