{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:22:25Z","timestamp":1793445745016,"version":"4.5.0"},"posted":{"date-parts":[[2024,7,10]]},"group-title":"Neuroscience","reference-count":91,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Corticotropin-releasing factor (CRF, encoded by\n                  <jats:italic>Crh<\/jats:italic>\n                  ) signaling is thought to play a critical role in the development of excessive alcohol drinking and the emotional and physical pain associated with alcohol withdrawal. Here, we investigated the parasubthalamic nucleus (PSTN) as a potential source of CRF relevant to the control of alcohol consumption, affect, and nociception in mice. We identified PSTN\n                  <jats:italic>Crh<\/jats:italic>\n                  neurons as a neuronal subpopulation that exerts a potent and unique influence on behavior by promoting not only alcohol but also saccharin drinking, while PSTN neurons are otherwise known to suppress consummatory behaviors. Furthermore, PSTN\n                  <jats:italic>Crh<\/jats:italic>\n                  neurons are causally implicated in the escalation of alcohol and saccharin intake produced by chronic intermittent ethanol (CIE) vapor inhalation, a mouse model of alcohol use disorder. In contrast to our predictions, the ability of PSTN\n                  <jats:italic>Crh<\/jats:italic>\n                  neurons to increase alcohol drinking is not mediated by CRF\n                  <jats:sub>1<\/jats:sub>\n                  signaling. Moreover, the pattern of behavioral disinhibition and reduced nociception driven by their activation does not support a role of negative reinforcement as a motivational basis for the concomitant increase in alcohol drinking. Finally, silencing\n                  <jats:italic>Crh<\/jats:italic>\n                  expression in the PSTN slowed down the escalation of alcohol intake in mice exposed to CIE and accelerated their recovery from withdrawal-induced mechanical hyperalgesia. Altogether, our results suggest that PSTN\n                  <jats:italic>Crh<\/jats:italic>\n                  neurons may represent an important node in the brain circuitry linking alcohol use disorder with sweet liking and novelty seeking.\n                <\/jats:p>","DOI":"10.1101\/2024.07.06.602357","type":"posted-content","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T21:15:23Z","timestamp":1720646123000},"source":"Crossref","is-referenced-by-count":0,"title":["Mouse parasubthalamic\n                  <i>Crh<\/i>\n                  neurons drive alcohol drinking escalation and behavioral disinhibition"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2136-6119","authenticated-orcid":false,"given":"Max","family":"Kreifeldt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0102-558X","authenticated-orcid":false,"given":"Agbonlahor","family":"Okhuarobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0397-4006","authenticated-orcid":false,"given":"Jeffery L","family":"Dunning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4693-7012","authenticated-orcid":false,"given":"Catherine","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7443-3026","authenticated-orcid":false,"given":"Giovana","family":"Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8767-3897","authenticated-orcid":false,"given":"Harpreet","family":"Sidhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4459-9540","authenticated-orcid":false,"given":"Candice","family":"Contet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"8","key":"2024071210100498000_2024.07.06.602357v1.1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of addiction: a neurocircuitry analysis","volume":"3","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"2024071210100498000_2024.07.06.602357v1.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.psych.59.103006.093548"},{"key":"2024071210100498000_2024.07.06.602357v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.06.006"},{"key":"2024071210100498000_2024.07.06.602357v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.09.008"},{"key":"2024071210100498000_2024.07.06.602357v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2012.07.010"},{"key":"2024071210100498000_2024.07.06.602357v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13507"},{"key":"2024071210100498000_2024.07.06.602357v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2007.03.009"},{"key":"2024071210100498000_2024.07.06.602357v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/acer.15228"},{"key":"2024071210100498000_2024.07.06.602357v1.9","doi-asserted-by":"crossref","unstructured":"Gilpin NW , Richardson HN , Cole M , Koob GF . 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