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People assigned female at birth and those with adverse childhood experiences are stress-vulnerable and more likely to report drinking as a means of \u201cself-medication.\u201d Prior studies in our laboratory showed that adolescent social isolation stress (SIS) increases vulnerability to ethanol (EtOH) intake and consumption despite negative consequences in female rats.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>Here, we explored modulation of the dorsal raphe nucleus (DRN)-serotonin (5-HT) system, a sexually dimorphic neurotransmitter system involved in stress-reward interactions, to determine its contribution to EtOH-motivated behaviors in rats that have undergone SIS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We employed electrophysiological and functional neuroanatomy strategies to show that both SIS and EtOH exposure induce persistent hypofunction of the DRN 5-HT system, particularly in females. Chemogenetic activation of DRN 5-HT neurons attenuated reward value for both EtOH and sucrose and elevated punished responding for EtOH in a stress-dependent manner.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results highlight an inverse relationship between EtOH consumption and the 5-HT system, the sex- and stress-dependent nature of this relationship, and a connection between DRN 5-HT signaling and acute responding to rewards and punishment. These data support the DRN 5-HT system as a potential target to treat aberrant alcohol consumption and drinking despite negative consequences in stress-vulnerable populations.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00213-025-06749-3","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:03:57Z","timestamp":1738645437000},"page":"763-781","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploring the effects of adolescent social isolation stress on the serotonin system and ethanol-motivated behaviors"],"prefix":"10.1007","volume":"242","author":[{"given":"Bryan D.","family":"McElroy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S.","family":"McCloskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber R.","family":"Alberici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5684-6716","authenticated-orcid":false,"given":"Lynn G.","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"issue":"6\u20137","key":"6749_CR1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.euroneuro.2006.08.009","volume":"17","author":"N Abumaria","year":"2007","unstructured":"Abumaria N, Rygula R, Hiemke C, Fuchs E, Havemann-Reinecke U, R\u00fcther E, Fl\u00fcgge G (2007) Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat. 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