Ortelli Olivia A, Weiner Jeffrey L
Wake Forest University School of Medicine, Department of Translational Neuroscience, United States.
Addict Neurosci. 2025 Mar;14. doi: 10.1016/j.addicn.2025.100196. Epub 2025 Jan 18.
Investigating how environmental factors, such as the availability of non-ethanol alternative reinforcers, influences ethanol self-administration is critical for understanding the pathology of alcohol use disorder (AUD). Here we established the first operant choice paradigm that leverages the strengths of the sipper tube self-administration model to investigate how concurrent access to sucrose altered ethanol self-administration in male and female Long Evans rats. Choice behavior was examined using two distinct paradigms, including a novel adaptation of the response requirement paradigm. Under both a fixed-ratio or response requirement paradigm, we observed that concurrent availability of an alternative reinforcer significantly reduced appetitive and consummatory ethanol drinking-related behaviors. Furthermore, we assessed the sensitivity of the response requirement choice paradigm by administering the pharmacological stressor yohimbine and by altering the taste of the ethanol solution. Yohimbine administration non-selectively increased ethanol and sucrose intake, but not seeking, while taste adulteration decreased ethanol seeking and intake. These experiments demonstrate the utility of two concurrent choice paradigms that can more accurately capture AUD-like phenotypes, such as ethanol-directed choice in the face of alternative reinforcers. Future studies should investigate how models of vulnerability and dependence alter ethanol choice behavior under these paradigms.
研究环境因素,如非乙醇替代强化物的可获得性,如何影响乙醇自我给药,对于理解酒精使用障碍(AUD)的病理机制至关重要。在此,我们建立了首个操作性选择范式,该范式利用吸管自我给药模型的优势,来研究同时给予蔗糖如何改变雄性和雌性长 Evans 大鼠的乙醇自我给药行为。使用两种不同的范式对选择行为进行了检测,其中包括对反应要求范式的一种新的改编。在固定比率或反应要求范式下,我们观察到替代强化物的同时存在显著减少了与乙醇饮用相关的食欲和摄食行为。此外,我们通过给予药理学应激源育亨宾以及改变乙醇溶液的味道,评估了反应要求选择范式的敏感性。给予育亨宾非选择性地增加了乙醇和蔗糖的摄入量,但不增加寻求行为,而味道掺假则减少了乙醇寻求和摄入量。这些实验证明了两种同时选择范式的实用性,它们能够更准确地捕捉类似 AUD 的表型,例如在面对替代强化物时对乙醇的定向选择。未来的研究应探讨易感性和依赖性模型如何在这些范式下改变乙醇选择行为。