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Neuropharmacology
2012 Aug 01;632:190-201. doi: 10.1016/j.neuropharm.2012.03.014.
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Ivermectin reduces alcohol intake and preference in mice.
Yardley MM
,
Wyatt L
,
Khoja S
,
Asatryan L
,
Ramaker MJ
,
Finn DA
,
Alkana RL
,
Huynh N
,
Louie SG
,
Petasis NA
,
Bortolato M
,
Davies DL
.
???displayArticle.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.
Amadio,
Mapping P2X and P2Y receptor proteins in striatum and substantia nigra: An immunohistological study.
2007, Pubmed
Amadio,
Mapping P2X and P2Y receptor proteins in striatum and substantia nigra: An immunohistological study.
2007,
Pubmed
Asatryan,
Implication of the purinergic system in alcohol use disorders.
2011,
Pubmed
Asatryan,
Ivermectin antagonizes ethanol inhibition in purinergic P2X4 receptors.
2010,
Pubmed
,
Xenbase
Bachmanov,
Chemosensory factors influencing alcohol perception, preferences, and consumption.
2003,
Pubmed
Belknap,
Voluntary consumption of ethanol in 15 inbred mouse strains.
1993,
Pubmed
Blednov,
Hybrid mice as genetic models of high alcohol consumption.
2010,
Pubmed
Blednov,
Perception of sweet taste is important for voluntary alcohol consumption in mice.
2008,
Pubmed
Bouchery,
Economic costs of excessive alcohol consumption in the U.S., 2006.
2011,
Pubmed
Boxall,
Veterinary medicines and the environment.
2005,
Pubmed
Buell,
An antagonist-insensitive P2X receptor expressed in epithelia and brain.
1996,
Pubmed
Burkhart,
Ivermectin: an assessment of its pharmacology, microbiology and safety.
2000,
Pubmed
Colombo,
The cannabinoid CB1 receptor antagonist, rimonabant, as a promising pharmacotherapy for alcohol dependence: preclinical evidence.
2007,
Pubmed
Davies,
The role of GABAA receptors in mediating the effects of alcohol in the central nervous system.
2003,
Pubmed
Davies,
Ethanol sensitivity in ATP-gated P2X receptors is subunit dependent.
2002,
Pubmed
,
Xenbase
Davies,
Ethanol differentially affects ATP-gated P2X(3) and P2X(4) receptor subtypes expressed in Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Davis,
Behavioral effects of ivermectin in mice.
1999,
Pubmed
Dawson,
Anticonvulsant and adverse effects of avermectin analogs in mice are mediated through the gamma-aminobutyric acid(A) receptor.
2000,
Pubmed
,
Xenbase
Di Chiara,
Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.
1988,
Pubmed
Edwards,
Ivermectin: does P-glycoprotein play a role in neurotoxicity?
2003,
Pubmed
Finn,
Reinstatement of ethanol and sucrose seeking by the neurosteroid allopregnanolone in C57BL/6 mice.
2008,
Pubmed
Finn,
Sex differences in the effect of ethanol injection and consumption on brain allopregnanolone levels in C57BL/6 mice.
2004,
Pubmed
Ford,
The influence of mecamylamine on ethanol and sucrose self-administration.
2009,
Pubmed
Ford,
Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice.
2007,
Pubmed
Ford,
Influence of reinforcement schedule on ethanol consumption patterns in non-food restricted male C57BL/6J mice.
2007,
Pubmed
Ford,
Ethanol intake patterns in female mice: influence of allopregnanolone and the inhibition of its synthesis.
2008,
Pubmed
Geary,
Ivermectin 20 years on: maturation of a wonder drug.
2005,
Pubmed
Gewiss,
Acamprosate and diazepam differentially modulate alcohol-induced behavioural and cortical alterations in rats following chronic inhalation of ethanol vapour.
1991,
Pubmed
Geyer,
Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice.
2009,
Pubmed
Gonzales,
The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement.
2004,
Pubmed
Grant,
The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991-1992 and 2001-2002.
2004,
Pubmed
Guzzo,
Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects.
2002,
Pubmed
Heilig,
Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms.
2006,
Pubmed
Jelínkova,
Identification of P2X(4) receptor transmembrane residues contributing to channel gating and interaction with ivermectin.
2008,
Pubmed
Jelínková,
Identification of P2X4 receptor-specific residues contributing to the ivermectin effects on channel deactivation.
2006,
Pubmed
Johnson,
Medication treatment of different types of alcoholism.
2010,
Pubmed
Johnson,
Topiramate for treating alcohol dependence: a randomized controlled trial.
2007,
Pubmed
Kampov-Polevoy,
Association between preference for sweets and excessive alcohol intake: a review of animal and human studies.
1999,
Pubmed
Khakh,
Allosteric control of gating and kinetics at P2X(4) receptor channels.
1999,
Pubmed
,
Xenbase
Kimpel,
Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions.
2007,
Pubmed
Koob,
Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory.
2009,
Pubmed
Kosten,
Pharmacologically targeting the P2rx4 gene on maintenance and reinstatement of alcohol self-administration in rats.
2011,
Pubmed
Krause,
Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor.
1998,
Pubmed
,
Xenbase
Krügel,
Purinergic modulation of neuronal activity in the mesolimbic dopaminergic system in vivo.
2003,
Pubmed
Lerchner,
Reversible silencing of neuronal excitability in behaving mice by a genetically targeted, ivermectin-gated Cl- channel.
2007,
Pubmed
Lespine,
Interaction of macrocyclic lactones with the multidrug transporters: the bases of the pharmacokinetics of lipid-like drugs.
2009,
Pubmed
Lespine,
Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship.
2007,
Pubmed
Lowery,
CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis.
2010,
Pubmed
McCLEARN,
The genetics of mouse behavior in novel situations.
1959,
Pubmed
Middaugh,
Operant ethanol reward in C57BL/6 mice: influence of gender and procedural variables.
1999,
Pubmed
Middaugh,
Ethanol consumption by C57BL/6 mice: influence of gender and procedural variables.
1999,
Pubmed
Molinari,
New ventures in the genotoxic and cytotoxic effects of macrocyclic lactones, abamectin and ivermectin.
2010,
Pubmed
Neasta,
Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders.
2010,
Pubmed
Omura,
Ivermectin: 25 years and still going strong.
2008,
Pubmed
Ostrovskaya,
Ethanol is a fast channel inhibitor of P2X4 receptors.
2011,
Pubmed
Perkins,
Molecular targets and mechanisms for ethanol action in glycine receptors.
2010,
Pubmed
Popova,
A point mutation in the ectodomain-transmembrane 2 interface eliminates the inhibitory effects of ethanol in P2X4 receptors.
2010,
Pubmed
,
Xenbase
Rhodes,
Mouse inbred strain differences in ethanol drinking to intoxication.
2007,
Pubmed
Rhodes,
Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice.
2005,
Pubmed
Richard-Lenoble,
Ivermectin and filariasis.
2003,
Pubmed
Roberts,
Estrous cycle effects on operant responding for ethanol in female rats.
1998,
Pubmed
Rodgers,
Research activities related to treatment of alcoholism.
1966,
Pubmed
Samson,
Appetitive and consummatory behaviors in the control of ethanol consumption: a measure of ethanol seeking behavior.
1998,
Pubmed
Samson,
Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats.
1986,
Pubmed
Samson,
A new assessment of the ability of oral ethanol to function as a reinforcing stimulus.
2000,
Pubmed
Sattelle,
Comparative pharmacology and computational modelling yield insights into allosteric modulation of human alpha7 nicotinic acetylcholine receptors.
2009,
Pubmed
,
Xenbase
Shan,
Ivermectin, an unconventional agonist of the glycine receptor chloride channel.
2001,
Pubmed
Silberberg,
Ivermectin Interaction with transmembrane helices reveals widespread rearrangements during opening of P2X receptor channels.
2007,
Pubmed
,
Xenbase
Soto,
P2X4: an ATP-activated ionotropic receptor cloned from rat brain.
1996,
Pubmed
,
Xenbase
Spinosa,
Possible anxiolytic effects of ivermectin in rats.
2002,
Pubmed
Steensland,
Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking.
2007,
Pubmed
Sun,
Effects of avermectins on neurite outgrowth in differentiating mouse neuroblastoma N2a cells.
2010,
Pubmed
Tabakoff,
Genetical genomic determinants of alcohol consumption in rats and humans.
2009,
Pubmed
Tanchuck,
Assessment of GABA-B, metabotropic glutamate, and opioid receptor involvement in an animal model of binge drinking.
2011,
Pubmed
Trailovic,
Central and peripheral neurotoxic effects of ivermectin in rats.
2011,
Pubmed
Vengeliene,
Neuropharmacology of alcohol addiction.
2008,
Pubmed
Weiss,
Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants.
1993,
Pubmed
Xiao,
Purinergic type 2 receptors at GABAergic synapses on ventral tegmental area dopamine neurons are targets for ethanol action.
2008,
Pubmed
Xiong,
The mechanism by which ethanol inhibits rat P2X4 receptors is altered by mutation of histidine 241.
2005,
Pubmed
,
Xenbase
Xiong,
Differential modulation by copper and zinc of P2X2 and P2X4 receptor function.
1999,
Pubmed
,
Xenbase
Xiong,
Inhibition by ethanol of rat P2X(4) receptors expressed in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Yoneyama,
Voluntary ethanol consumption in 22 inbred mouse strains.
2008,
Pubmed
