Timme Nicholas M, Ardinger Cherish E, Weir Seth D C, Zelaya-Escobar Rachel, Kruger Rachel, Lapish Christopher C
Department of Psychology, Indiana University - Purdue University Indianapolis, 402 N. Blackford St, LD 124, Indianapolis, IN, 46202, USA.
Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MSB 5035, Indianapolis, IN, 46202, USA.
bioRxiv. 2023 Oct 5:2023.06.20.545767. doi: 10.1101/2023.06.20.545767.
A key facet of alcohol use disorder is continuing to drink alcohol despite negative consequences (so called "aversion-resistant drinking"). In this study, we sought to assess the degree to which head-fixed mice exhibit aversion-resistant drinking and to leverage behavioral analysis techniques available in head-fixture to relate non-consummatory behaviors to aversion-resistant drinking. We assessed aversion-resistant drinking in head-fixed female and male C57BL/6J mice. We adulterated 20% (v/v) alcohol with varying concentrations of the bitter tastant quinine to measure the degree to which mice would continue to drink despite this aversive stimulus. We recorded high-resolution video of the mice during head-fixed drinking, tracked body parts with machine vision tools, and analyzed body movements in relation to consumption. Female and male head-fixed mice exhibited heterogenous levels of aversion-resistant drinking. Additionally, non-consummatory behaviors, such as paw movement and snout movement, were related to the intensity of aversion-resistant drinking. These studies demonstrate that head-fixed mice exhibit aversion-resistant drinking and that non-consummatory behaviors can be used to assess perceived aversiveness in this paradigm. Furthermore, these studies lay the groundwork for future experiments that will utilize advanced electrophysiological techniques to record from large populations of neurons during aversion-resistant drinking to understand the neurocomputational processes that drive this clinically relevant behavior.
酒精使用障碍的一个关键方面是尽管存在负面后果仍继续饮酒（即所谓的“抗厌恶饮酒”）。在本研究中，我们试图评估头部固定的小鼠表现出抗厌恶饮酒的程度，并利用头部固定装置中可用的行为分析技术，将非摄食行为与抗厌恶饮酒联系起来。我们评估了头部固定的雌性和雄性C57BL/6J小鼠的抗厌恶饮酒情况。我们用不同浓度的苦味剂奎宁掺假20%（v/v）酒精，以测量小鼠在这种厌恶刺激下仍会继续饮酒的程度。我们在头部固定饮酒期间记录了小鼠的高分辨率视频，用机器视觉工具跟踪身体部位，并分析了与饮酒相关的身体运动。头部固定的雌性和雄性小鼠表现出不同程度的抗厌恶饮酒。此外，非摄食行为，如爪子运动和口鼻运动，与抗厌恶饮酒的强度有关。这些研究表明，头部固定的小鼠表现出抗厌恶饮酒，并且非摄食行为可用于评估该范式下的感知厌恶程度。此外，这些研究为未来的实验奠定了基础，这些实验将利用先进的电生理技术在抗厌恶饮酒期间记录大量神经元的活动，以了解驱动这种临床相关行为的神经计算过程。
