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纳曲酮对C57BL/6J小鼠酒精、蔗糖和糖精暴饮样饮酒行为的影响:一项采用多瓶选择程序的研究

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure.

作者信息

Morales Ileana, Rodríguez-Borillo Olga, Font Laura, Pastor Raúl

机构信息

Department of Psychology, University of Michigan, Ann Arbor, Michigan, USA.

Area de Psicobiología, Universitat Jaume I, Castellón, Spain.

出版信息

Behav Pharmacol. 2020 Apr;31(2&3):256-271. doi: 10.1097/FBP.0000000000000553.

Abstract

Chronic alcohol (ethyl alcohol, EtOH) binging has been associated with long-term neural adaptations that lead to the development of addiction. Many of the neurobiological features of EtOH abuse are shared with other forms of binging, like pathological feeding. The drinking-in-the-dark (DID) paradigm has been used extensively to study the neurobiology of EtOH binge-like drinking due to its ability to promote high intakes relevant to human behavior. DID can also generate high consumption of other tastants, but this procedure has not been fully adapted to study forms of binging behavior that are not alcohol-driven. In the present study, we used a modified version of DID that uses multiple bottle availability to promote even higher levels of EtOH drinking in male C57BL/6J mice and allows a thorough investigation of tastant preferences. We assessed whether administration of systemic naltrexone could reduce binging on EtOH, sucrose, and saccharin separately as well as in combination. Our multiple bottle DID procedure resulted in heightened levels of consumption compared with previously reported data using this task. We found that administration of the opioid receptor antagonist naltrexone reduced intakes of preferred, highly concentrated EtOH, sucrose, and saccharin. We also report that naltrexone was able to reduce overall intakes when animals were allowed to self-administer EtOH, sucrose, or saccharin in combination. Our modified DID procedure provides a novel approach to study binging behavior that extends beyond EtOH to other tastants (i.e. sucrose and artificial sweeteners), and has implications for the study of the neuropharmacology of binge drinking.

摘要

长期酗酒(饮用乙醇,EtOH)与导致成瘾的长期神经适应性变化有关。乙醇滥用的许多神经生物学特征与其他形式的暴饮暴食(如病理性进食)相同。由于“黑暗中饮酒”(DID)范式能够促进与人类行为相关的高摄入量,因此已被广泛用于研究乙醇暴饮样饮酒的神经生物学。DID也会导致对其他味觉剂的高摄入量,但该方法尚未完全适用于研究非酒精驱动的暴饮暴食行为。在本研究中,我们使用了一种改良版的DID,该方法利用多个瓶子来促进雄性C57BL/6J小鼠更高水平的乙醇饮用,并允许全面研究味觉剂偏好。我们评估了全身注射纳曲酮是否能分别以及联合减少对乙醇、蔗糖和糖精的暴饮。与此前使用该任务所报告的数据相比,我们的多瓶DID程序导致了更高的摄入量。我们发现,注射阿片受体拮抗剂纳曲酮可减少对偏好的、高浓度乙醇、蔗糖和糖精的摄入量。我们还报告称,当动物被允许联合自行摄入乙醇、蔗糖或糖精时,纳曲酮能够减少总体摄入量。我们改良的DID程序提供了一种新的方法来研究暴饮暴食行为,这种行为不仅限于乙醇,还扩展到其他味觉剂(即蔗糖和人工甜味剂),并对暴饮的神经药理学研究具有启示意义。

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