Gálvez Gabriel, González-Gutiérrez Juan Pablo, Hödar-Salazar Martín, Sotomayor-Zárate Ramón, Quintanilla María Elena, Quilaqueo María Elena, Rivera-Meza Mario, Iturriaga-Vásquez Patricio
Laboratory of Experimental Pharmacology, Faculty of Chemical Sciences and Pharmacy, University of Chile, Santiago 8380494, Chile.
Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Talca 3467987, Chile.
Biomedicines. 2022 Jun 22;10(7):1482. doi: 10.3390/biomedicines10071482.
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.
酗酒是一个全球性的公共卫生问题，经济成本高昂，且会影响健康和社会行为。据估计，全球每年有300万人死于酗酒，而在智利，每年约有9000人因此死亡。烟碱型乙酰胆碱受体（nAChRs）是在中枢神经系统中表达的配体门控离子通道，有人认为它们可调节与滥用和依赖有关的乙醇作用机制。先前的研究表明，用nAChRs拮抗剂UFR2709进行短期治疗，可在智利大学嗜酒（UChB）大鼠中采用双瓶自由选择范式减少乙醇摄入量。在此，我们提供了UFR2709在减少乙醇获取和长期乙醇消耗方面有效性的证据。我们的结果表明，UFR2709（腹腔注射2.5mg/kg）可减少寻觅行为和乙醇摄入量，即使在停止给药后也是如此，并使总体乙醇摄入量减少了约55%。使用未接触过乙醇的UChB嗜酒大鼠，我们证明UFR2709可以延迟并减少寻求和饮用乙醇的遗传适应性冲动，并防止其过量摄入。
