{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:32:20Z","timestamp":1785407540428,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,18]]},"group-title":"Neuroscience","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R00AA027835"],"award-info":[{"award-number":["R00AA027835"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The gene\n                  <jats:italic>DPP6<\/jats:italic>\n                  has been associated with behavioral phenotypes of alcohol use disorder (AUD) in recent human genome wide association studies.\n                  <jats:italic>DPP6<\/jats:italic>\n                  encodes an auxiliary subunit that modulates A-type voltage-gated potassium channels, particularly Kv4.2. To further assess the role of this gene in ethanol-related traits, we tested\n                  <jats:italic>Dpp6<\/jats:italic>\n                  knockout (KO) mice for ethanol conditioned place preference (CPP), locomotor activity, and ethanol-induced anxiolysis. Male homozygous KO mice (HOM) showed greater preference for the ethanol-paired context compared to wild type littermates (WT) and heterozygous KO mice (HET), while female mice showed no genotypic difference. HOM of both sexes exhibited greater novelty-induced hyperactivity in the CPP apparatus than HET and WT mice in the first two minutes. In a separate experiment, HOM mice showed enhanced locomotor activity following a 1.5 g\/kg ethanol injection; however, they also displayed greater locomotor activity during habituation, suggesting basal locomotor differences. Following 1.5 and 2 g\/kg injections, HOM mice exhibited EtOH-induced anxiolysis in the first 5 minutes, while the HET and WT mice did not. Lastly, HOM mice displayed a significant sedative response compared to WT animals following a 2 g\/kg injection of ethanol. Ultimately, these findings validate a role for\n                  <jats:italic>Dpp6<\/jats:italic>\n                  in modulating ethanol\u2019s rewarding, anxiolytic, and sedative effects in a sex-dependent manner.\n                <\/jats:p>","DOI":"10.1101\/2025.08.15.670589","type":"posted-content","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T14:45:14Z","timestamp":1755528314000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Dpp6<\/i>\n                  Knockout Mice Exhibit Increased Ethanol Conditioned Place Preference and Acute Ethanol-Induced Anxiolytic Behavior"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8064-636X","authenticated-orcid":false,"given":"Maribel","family":"Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Deparment of Pharmaceutical Sciences - University of New Mexico Health Sciences Center Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-7578","authenticated-orcid":false,"given":"Amanda M","family":"Barkley-Levenson","sequence":"additional","affiliation":[{"name":"Deparment of Pharmaceutical Sciences - University of New Mexico Health Sciences Center Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020510515609000_2025.08.15.670589v2.1","unstructured":"2023 NSDUH Detailed Tables | CBHSQ Data [WWW Document], n.d. 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