Biomedicines (Jun 2022)

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

  • Gabriel Gálvez,
  • Juan Pablo González-Gutiérrez,
  • Martín Hödar-Salazar,
  • Ramón Sotomayor-Zárate,
  • María Elena Quintanilla,
  • María Elena Quilaqueo,
  • Mario Rivera-Meza,
  • Patricio Iturriaga-Vásquez

DOI
https://doi.org/10.3390/biomedicines10071482
Journal volume & issue
Vol. 10, no. 7
p. 1482

Abstract

Read online

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 naïve 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.

Keywords