biostudies-literatureHaun HNational Institute on Alcohol Abuse and AlcoholismNIAAA NIH HHSNational Institutes of Health115482https://www.ebi.ac.uk/biostudies/studies/S-EPMC12181985biostudies-literatureUnknown44(4)High-intensity alcohol drinking during binge episodes contributes to the socioeconomic burden created by alcohol use disorders (AUDs), and nociceptin receptor (NOP) antagonists have emerged as a promising intervention. To better understand the contribution of the NOP system to binge drinking, we found that nociceptin-containing neurons of the lateral septum (LS^Pnoc) displayed increased excitability during withdrawal from binge-like alcohol drinking. LS^Pnoc activation promoted active avoidance and potentiated binge-like drinking behavior, whereas silencing of this population reduced alcohol drinking. LS^Pnoc form robust monosynaptic inputs locally within the LS and genetic deletion of NOP or microinjection of a NOP antagonist into the LS decreased alcohol intCell reportsSepto-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.PMC12181985F32AA030494F32AA031395R01 AA019454F32 AA031395F32 AA030494P60 AA011605K99 AA030628P60AA011605U01AA020911U01 AA020911T32AA007573T32 AA007573Haun HRoland AYan LLee SFlanigan MKash THernandez RHon OTaxier LMendez HfalseSepto-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.High-intensity alcohol drinking during binge episodes contributes to the socioeconomic burden created by alcohol use disorders (AUDs), and nociceptin receptor (NOP) antagonists have emerged as a promising intervention. To better understand the contribution of the NOP system to binge drinking, we found that nociceptin-containing neurons of the lateral septum (LS^Pnoc) displayed increased excitability during withdrawal from binge-like alcohol drinking. LS^Pnoc activation promoted active avoidance and potentiated binge-like drinking behavior, whereas silencing of this population reduced alcohol drinking. LS^Pnoc form robust monosynaptic inputs locally within the LS and genetic deletion of NOP or microinjection of a NOP antagonist into the LS decreased alcohol int2025-01-01T00:00:00Z2025 Apr2026-05-29T14:29:10.186Z2026-04-08T05:04:12.434ZS-EPMC121819854015343610.1016/j.celrep.2025.115482