UFR2709, an Antagonist of Nicotinic Acetylcholine Receptors, Delays the Acquisition and Reduces Long-Term Ethanol Intake in Alcohol-Preferring UChB Bibulous Rats

Galvez, Gabriel; Gonzalez-Gutierrez, Juan Pablo; Hodar-Salazar, Martin; Sotomayor-Zarate, Ramon; Quintanilla, Maria Elena; Quilaqueo, Maria Elena; Rivera-Meza, Mario; Iturriaga-Vasquez, Patricio

Abstract

Alcoholism is a worldwide public health problem with high economic cost and which affects health and social behavior. It is estimated that alcoholism kills 3 million people globally, while in Chile it is responsible for around 9 thousand deaths per year. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels expressed in the central nervous system, and they were suggested to modulate the ethanol mechanism involved in abuse and dependence. Previous work demonstrated a short-term treatment with UFR2709, a nAChRs antagonist, which reduced ethanol intake using a two-bottle free-choice paradigm in University of Chile bibulous (UChB) rats. Here, we present evidence of the UFR2709 efficacy in reducing the acquisition and long-term ethanol consumption. Our results show that UFR2709 (2.5 mg/kg i.p.) reduces the seek behavior and ethanol intake, even when the drug administration was stopped, and induced a reduction in the overall ethanol intake by around 55%. Using naive UChB bibulous rats, we demonstrate that UFR2709 could delay and reduce the genetically adaptive impulse to seek and drink ethanol and prevent its excessive intake.

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Título según WOS: ID WOS:000833892500001 Not found in local WOS DB
Título de la Revista: BIOMEDICINES
Volumen: 10
Número: 7
Editorial: MDPI
Fecha de publicación: 2022
DOI:

10.3390/biomedicines10071482

Notas: ISI