title: Ivermectin reduces alcohol intake and preference in mice.
abstract: The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25-10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (C(max)) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Yardley
authors.forename: Letisha
authors.initials: L
authors.lastname: Wyatt
authors.forename: Sheraz
authors.initials: S
authors.lastname: Khoja
authors.forename: Liana
authors.initials: L
authors.lastname: Asatryan
authors.forename: Marcia J
authors.initials: MJ
authors.lastname: Ramaker
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Finn
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Alkana
authors.forename: Nhat
authors.initials: N
authors.lastname: Huynh
authors.forename: Stan G
authors.initials: SG
authors.lastname: Louie
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Davies
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007559:Ivermectin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012646:Self Administration; D012737:Sex Factors
chemical_list: D000977:Antiparasitic Agents; D000431:Ethanol; D007559:Ivermectin