{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:04:09Z","timestamp":1793466249606,"version":"4.5.0"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"crossref","award":["AA027700 (MR),AA013498 (MR),P60 AA006420 (MR),AA017447 (MR"],"award-info":[{"award-number":["AA027700 (MR),AA013498 (MR),P60 AA006420 (MR),AA017447 (MR"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"crossref","award":["RC),AA021491 (MR),AA029841 (MR),K99 AA030609 (VV),T32 AA007456 (BC"],"award-info":[{"award-number":["RC),AA021491 (MR),AA029841 (MR),K99 AA030609 (VV),T32 AA007456 (BC"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"crossref","award":["CS),K99 AA031718 (BC),AA013519 (ARO),AA010760 (ARO),as well as the U.S. Department of Veteran Affairs (I01 BX004699 to ARO)"],"award-info":[{"award-number":["CS),K99 AA031718 (BC),AA013519 (ARO),AA010760 (ARO),as well as the U.S. Department of Veteran Affairs (I01 BX004699 to ARO)"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:p>\n                    The FDA-approved phosphodiesterase type 4 (PDE4) inhibitor, apremilast, has been recently investigated as a pharmacotherapy for alcohol use disorder (AUD) with promising efficacy in rodent models and humans. However, apremilast\u2019s effects on mechanical allodynia associated with AUD as well as distinct responses of this drug between males and females are understudied. The present study examined the behavioral and electrophysiological effects of apremilast in Marchigian Sardinian alcohol-preferring (msP) rats and their Wistar counterparts. We used a 2\u2013bottle choice (2-BC) alcohol drinking procedure and tested mechanical sensitivity across our drinking regimen. Spontaneous inhibitory GABA-mediated postsynaptic currents from the central nucleus of the amygdala (CeA) following apremilast application were tested in a subset of rats using ex vivo electrophysiology. Transcript levels for\n                    <jats:italic>Pde4a<\/jats:italic>\n                    or -\n                    <jats:italic>4b<\/jats:italic>\n                    subtypes were assessed for their modulation by alcohol. Apremilast reduced alcohol drinking in both strains of rats. Apremilast reduced mechanical allodynia immediately after drinking, persisting into early and late abstinence. Apremilast increased GABAergic transmission in CeA slices of alcohol-exposed Wistars but not msP rats, suggesting neuroadaptations in msPs by excessive drinking and mechanical allodynia.\n                    <jats:italic>Pde4<\/jats:italic>\n                    subtype transcript levels were increased in CeA by alcohol. These results suggest that apremilast alleviates co-occurring excessive drinking and pain sensitivity, and they further confirm PDE4\u2019s role in pain-associated AUD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189732","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T14:00:44Z","timestamp":1745244044000},"source":"Crossref","is-referenced-by-count":13,"title":["Apremilast reduces co-occurring alcohol drinking and mechanical allodynia and regulates central amygdala GABAergic transmission"],"prefix":"10.1172","volume":"10","author":[{"given":"Valentina","family":"Vozella","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Scripps Research Institute, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Borgonetti","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Scripps Research Institute, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Scripps Research Institute, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celsey M. 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