Nippert Kathryn E, Rowland Courtney P, Vazey Elena M, Moorman David E
Neuroscience and Behavior Graduate Program, University of Massachusetts Amherst, Amherst, MA, 01003, USA.
Department of Biology, University of Massachusetts Amherst, Amherst, MA, 01003, USA.
Neuropharmacology. 2024 Dec 1;260:110114. doi: 10.1016/j.neuropharm.2024.110114. Epub 2024 Aug 10.
Cognitive flexibility enables individuals to alter their behavior in response to changing environmental demands, facilitating optimal behavior in a dynamic world. The inability to do this, called behavioral inflexibility, is a pervasive behavioral phenotype in alcohol use disorder (AUD), driven by disruptions in cognitive flexibility. Research has repeatedly shown that behavioral inflexibility not only results from alcohol exposure across species but can itself be predictive of future drinking. Like many high-level executive functions, flexible behavior requires healthy functioning of the prefrontal cortex (PFC). The scope of this review addresses two primary themes: first, we outline tasks that have been used to investigate flexibility in the context of AUD or AUD models. We characterize these based on the task features and underlying cognitive processes that differentiate them from one another. We highlight the neural basis of flexibility measures, focusing on the PFC, and how acute or chronic alcohol in humans and non-human animal models impacts flexibility. Second, we consolidate findings on the molecular, physiological and functional changes in the PFC elicited by alcohol, that may contribute to cognitive flexibility deficits seen in AUD. Collectively, this approach identifies several key avenues for future research that will facilitate effective treatments to promote flexible behavior in the context of AUD, to reduce the risk of alcohol related harm, and to improve outcomes following AUD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".
认知灵活性使个体能够根据不断变化的环境需求改变其行为，从而在动态的世界中促进最优行为。无法做到这一点，即行为不灵活性，是酒精使用障碍（AUD）中一种普遍存在的行为表型，由认知灵活性的破坏所驱动。研究反复表明，行为不灵活性不仅源于跨物种的酒精暴露，而且其本身可以预测未来的饮酒行为。与许多高级执行功能一样，灵活行为需要前额叶皮质（PFC）的健康运作。本综述的范围涉及两个主要主题：第一，我们概述了用于在AUD或AUD模型背景下研究灵活性的任务。我们根据任务特征和将它们彼此区分开来的潜在认知过程对这些任务进行了表征。我们强调灵活性测量的神经基础，重点关注PFC，以及人类和非人类动物模型中的急性或慢性酒精如何影响灵活性。第二，我们汇总了关于酒精引起的PFC分子、生理和功能变化的研究结果，这些变化可能导致AUD中出现的认知灵活性缺陷。总体而言，这种方法确定了未来研究的几个关键途径，这些途径将有助于开发有效的治疗方法，以促进AUD背景下的灵活行为，降低与酒精相关的伤害风险，并改善AUD后的治疗效果。本文是“精神疾病及相关模型中的PFC电路功能”特刊的一部分。
