title: Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.
abstract: Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans.
authors.affiliation: aDepartment of Pharmacology and Pharmaceutical Sciences bTitus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy cDepartment of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Yardley
authors.forename: Michael
authors.initials: M
authors.lastname: Neely
authors.forename: Nhat
authors.initials: N
authors.lastname: Huynh
authors.forename: Liana
authors.initials: L
authors.lastname: Asatryan
authors.forename: Stan G
authors.initials: SG
authors.lastname: Louie
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Alkana
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Davies
mesh_terms: D000427:Alcohol Deterrents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000428:Alcohol Drinking / Q000188:drug therapy*; D000704:Analysis of Variance; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002755:Choice Behavior / Q000187:drug effects; D002853:Chromatography, Liquid; D004327:Drinking Behavior / Q000187:drug effects; D060766:Drinking Water / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage; D005518:Food Preferences / Q000187:drug effects; D007559:Ivermectin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008810:Mice, Inbred C57BL; D053719:Tandem Mass Spectrometry
chemical_list: D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D060766:Drinking Water; D000431:Ethanol; D007559:Ivermectin