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Corticotrophin releasing factor (CRF), a stress-related neuropeptide, has been implicated in binge ethanol intake and ethanol dependence in rodents. CRF containing neurons in the bed nucleus of the stria terminalis (BNST\n                    <jats:sup>CRF<\/jats:sup>\n                    ) can influence ethanol consumption. These BNST\n                    <jats:sup>CRF<\/jats:sup>\n                    neurons also release GABA, raising the question, is it CRF release, GABA release, or both that is regulating alcohol consumption. Here, we used viral vectors to separate the effects of CRF and GABA release from BNST\n                    <jats:sup>CRF<\/jats:sup>\n                    neurons on the escalation of ethanol intake in an operant self-administration procedure in male and female mice. We found that CRF deletion in BNST neurons reduces ethanol intake in both sexes, with a stronger effect in males. For sucrose self-administration there was no effect of CRF deletion. Suppression of GABA release, via knockdown of vGAT, from BNST\n                    <jats:sup>CRF<\/jats:sup>\n                    produced a transient increase in ethanol operant self-administration in male mice, and reduced motivation to work for sucrose on a progressive ratio schedule of reinforcement in a sex-dependent manner. Together, these results highlight how different signaling molecules from the same populations of neurons can bidirectionally control behavior. Moreover, they suggest that BNST CRF release is important for high intensity ethanol drinking that precedes dependence, whereas GABA release from these neurons may play a role in regulating motivation.\n                  <\/jats:p>","DOI":"10.1038\/s41386-025-02192-2","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T09:28:37Z","timestamp":1757150917000},"page":"2040-2050","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Disentangling the effects of corticotrophin releasing factor and GABA release from the bed nucleus of the stria terminalis on ethanol self-administration in mice"],"prefix":"10.1038","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7662-8636","authenticated-orcid":false,"given":"Carol A.","family":"Gianessi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold L.","family":"Haun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-4871","authenticated-orcid":false,"given":"Dipa","family":"Pati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tori","family":"Sides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem P.","family":"Kelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graydon B.","family":"Gereau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Boyt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde W.","family":"Hodge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-4495","authenticated-orcid":false,"given":"Thomas L.","family":"Kash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"2192_CR1","unstructured":"Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and Health (NSDUH)|CBHSQ Data. https:\/\/www.samhsa.gov\/data\/sites\/default\/files\/NSDUH-FRR1-2014\/NSDUH-FRR1-2014.pdf."},{"key":"2192_CR2","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1081\/ADA-200032331","volume":"30","author":"KM Jennison","year":"2004","unstructured":"Jennison KM. 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