Involvement of Purinergic P2X4 Receptors in Alcohol Intake of High-Alcohol-Drinking (HAD) Rats

Alcoholism, Clinical and Experimental Research
Kelle M FranklinW J McBride

Abstract

The P2X4 receptor (P2X4R) is thought to be involved in regulating alcohol-consuming behaviors, and ethanol (EtOH) has been reported to inhibit P2X4Rs. Ivermectin is an antiparasitic agent that acts as a positive allosteric modulator of the P2X4R. This study examined the effects of systemically and centrally administered ivermectin on alcohol drinking of replicate lines of high-alcohol-drinking (HAD-1/HAD-2) rats, and the effects of lentiviral-delivered short-hairpin RNAs (shRNAs) targeting P2rx4 on EtOH intake of female HAD-2 rats. For the first experiment, adult male HAD-1 and HAD-2 rats were given 24-hour free-choice access to 15% EtOH versus water. Dose-response effects of ivermectin (1.5 to 7.5 mg/kg, intraperitoneally [i.p.]) on EtOH intake were determined; the effects of ivermectin were then examined for 2% w/v sucrose intake over 5 consecutive days. In the second experiment, female HAD-2 rats were trained to consume 15% EtOH under 2-hour limited access conditions, and dose-response effects of intracerebroventricular (ICV) administration of ivermectin (0.5 to 2.0 μg) were determined over 5 consecutive days. The third experiment determined the effects of microinfusion of a lentivirus expressing P2rx4 shRNAs into the poster...Continue Reading

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Citations

May 15, 2016·Alcoholism, Clinical and Experimental Research·Chelsea R Kasten, Stephen L Boehm
May 4, 2018·Expert Opinion on Investigational Drugs·Sarah S Ch'ng, Andrew J Lawrence
Sep 6, 2020·Neuroscience Bulletin·Alexia DuveauEric Boué-Grabot
Dec 14, 2018·Molecular Pharmacology·Kshitija DhunaLeanne Stokes
Jun 8, 2017·Frontiers in Pharmacology·Leanne StokesSamuel J Fountain
Jul 12, 2020·The Journal of Steroid Biochemistry and Molecular Biology·Sonja SivcevHana Zemkova
Apr 27, 2021·Frontiers in Immunology·Jean M KanellopoulosDavid M Ojcius

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