Ivermectin reduces alcohol intake and preference in mice

Megan M. Yardley, Letisha Wyatt, Sheraz Khoja, Liana Asatryan, Marcia J. Ramaker, Deborah (Deb) Finn, Ronald L. Alkana, Nhat Huynh, Stan G. Louie, Nicos A. Petasis, Marco Bortolato, Daryl L. Davies

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 (Cmax) 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.

Original languageEnglish (US)
Pages (from-to)190-201
Number of pages12
JournalNeuropharmacology
Volume63
Issue number2
DOIs
StatePublished - Aug 2012

Fingerprint

Ivermectin
Alcohols
Self Administration
Alcohol Drinking
Purinergic P2X4 Receptors
Ethanol
Binge Drinking
Saccharin
Anthelmintics
Xenopus
Inbred C57BL Mouse
Oocytes
Sucrose
Safety
Brain
Therapeutics

Keywords

  • Alcohol use disorders
  • Alcoholism therapy
  • Animal models
  • Drug repurposing
  • Ethanol

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Yardley, M. M., Wyatt, L., Khoja, S., Asatryan, L., Ramaker, M. J., Finn, D. D., ... Davies, D. L. (2012). Ivermectin reduces alcohol intake and preference in mice. Neuropharmacology, 63(2), 190-201. https://doi.org/10.1016/j.neuropharm.2012.03.014

Ivermectin reduces alcohol intake and preference in mice. / Yardley, Megan M.; Wyatt, Letisha; Khoja, Sheraz; Asatryan, Liana; Ramaker, Marcia J.; Finn, Deborah (Deb); Alkana, Ronald L.; Huynh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Bortolato, Marco; Davies, Daryl L.

In: Neuropharmacology, Vol. 63, No. 2, 08.2012, p. 190-201.

Research output: Contribution to journalArticle

Yardley, MM, Wyatt, L, Khoja, S, Asatryan, L, Ramaker, MJ, Finn, DD, Alkana, RL, Huynh, N, Louie, SG, Petasis, NA, Bortolato, M & Davies, DL 2012, 'Ivermectin reduces alcohol intake and preference in mice', Neuropharmacology, vol. 63, no. 2, pp. 190-201. https://doi.org/10.1016/j.neuropharm.2012.03.014
Yardley MM, Wyatt L, Khoja S, Asatryan L, Ramaker MJ, Finn DD et al. Ivermectin reduces alcohol intake and preference in mice. Neuropharmacology. 2012 Aug;63(2):190-201. https://doi.org/10.1016/j.neuropharm.2012.03.014
Yardley, Megan M. ; Wyatt, Letisha ; Khoja, Sheraz ; Asatryan, Liana ; Ramaker, Marcia J. ; Finn, Deborah (Deb) ; Alkana, Ronald L. ; Huynh, Nhat ; Louie, Stan G. ; Petasis, Nicos A. ; Bortolato, Marco ; Davies, Daryl L. / Ivermectin reduces alcohol intake and preference in mice. In: Neuropharmacology. 2012 ; Vol. 63, No. 2. pp. 190-201.
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