2. Academic Validation
  3. UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats

UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats

  • Front Pharmacol. 2019 Dec 3;10:1429. doi: 10.3389/fphar.2019.01429.
Gabriel Quiroz 1,  Ramón Sotomayor-Zárate 2,  Juan Pablo González-Gutierrez 3,  Franco Vizcarra 4,  Felipe Moraga 4,  Isabel Bermudez 5,  Miguel Reyes-Parada 6 7,  María Elena Quintanilla 8,  Diego Lagos 9,  Mario Rivera-Meza 9,  Patricio Iturriaga-Vásquez 4 10
Affiliations

Affiliations

  • 1 Programa de Doctorado en Farmacología, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
  • 2 Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
  • 3 Programa de Doctorado en Química, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
  • 4 Laboratorio de Síntesis Orgánica y Farmacología Molecular, Departamento de Ciencias Químicas y Recursos Naturales, Facultad de Ingeniería y Ciencias, Universidad de la Frontera, Temuco, Chile.
  • 5 Deptartment of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Oxford, United Kingdom.
  • 6 Centro de Investigación Biomédica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago, Chile.
  • 7 Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
  • 8 Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • 9 Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
  • 10 Center of Excellence in Biotechnology Research Applied to the Environment, Universidad de La Frontera, Temuco, Chile.
PMID: 31849674 DOI: 10.3389/fphar.2019.01429
Abstract

Brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric acetylcholine-gated cation channels, have been suggested as molecular targets for the treatment of alcohol abuse and dependence. Here, we examined the effect of the competitive nAChR antagonist UFR2709 on the alcohol consumption of high-alcohol-drinking UChB rats. UChB rats were given free access to ethanol for 24-h periods in a two-bottle free choice paradigm and their ethanol and water intake were measured. The Animals were i.p. injected daily for 17 days with a 10, 5, 2.5, or 1 mg/kg dose of UFR2709. Potential confounding motor effects of UFR2709 were assessed by examining the locomotor activity of Animals administered the highest dose of UR2709 tested (10 mg/kg i.p.). UFR2709 reduced ethanol consumption and ethanol preference and increased water consumption in a dose-dependent manner. The most effective dose of UFR2709 was 2.5 mg/kg, which induced a 56% reduction in alcohol consumption. Administration of UFR2709 did not affect the weight or locomotor activity of the rats, suggesting that its effects on alcohol consumption and preference were mediated by specific nAChRs.

Keywords

UChB rats; alcohol dependence; ethanol; nAChR antagonism; voluntary ethanol drinking.

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