biostudies-literatureQuijano Carde NANIDA NIH HHSNIAAA NIH HHSNational Institutes of HealthNIAAANIDANIGMS NIH HHSNIGMS108783https://www.ebi.ac.uk/biostudies/studies/S-EPMC8572579biostudies-literatureUnknown199Alcohol use disorder (AUD) is a neuropsychiatric condition affecting millions of people worldwide. Topiramate (TPM) is an antiepileptic drug that has been shown to reduce ethanol drinking in humans. However, TPM is associated with a variety of adverse effects due to its interaction with many receptor systems and intracellular pathways. GluK1-containing kainate receptors (GluK1*KARs) are non-selectively inhibited by TPM, and genetic association studies suggest that this receptor system could be targeted to reduce drinking in AUD patients. We examined the efficacy of LY466195, a selective inhibitor of GluK1*KAR, in reducing ethanol consumption in the intermittent two-bottle choice paradigm in mice. The effect of LY466195 on various ethanol-related phenotypes was investigated by quantificatioNeuropharmacologyAntagonism of GluK1-containing kainate receptors reduces ethanol consumption by modulating ethanol reward and withdrawal.PMC8572579T32 GM008076DA 036572R01 AA023192U01 AA025931T32GM008076K12 GM081259K12GM081259R01 DA036572De Biasi MFeinn RQuijano Carde NAKranzler HRPerez EEfalseAntagonism of GluK1-containing kainate receptors reduces ethanol consumption by modulating ethanol reward and withdrawal.Alcohol use disorder (AUD) is a neuropsychiatric condition affecting millions of people worldwide. Topiramate (TPM) is an antiepileptic drug that has been shown to reduce ethanol drinking in humans. However, TPM is associated with a variety of adverse effects due to its interaction with many receptor systems and intracellular pathways. GluK1-containing kainate receptors (GluK1*KARs) are non-selectively inhibited by TPM, and genetic association studies suggest that this receptor system could be targeted to reduce drinking in AUD patients. We examined the efficacy of LY466195, a selective inhibitor of GluK1*KAR, in reducing ethanol consumption in the intermittent two-bottle choice paradigm in mice. The effect of LY466195 on various ethanol-related phenotypes was investigated by quantificatio2021-01-01T00:00:00Z2021 Nov2026-05-31T16:00:16.925Z2025-04-04T12:46:10.176ZS-EPMC85725793450949710.1016/j.neuropharm.2021.108783