Department of Psychology, University of California San Diego, La Jolla, CA 92093, United States.
The Neurosciences Graduate Program, University of California San Diego, La Jolla, CA 92093, United States.
Alcohol. 2022 Jun;101:53-64. doi: 10.1016/j.alcohol.2022.03.004. Epub 2022 Apr 8.
Dysfunctional decision-making has been observed in alcohol dependence. However, the specific underlying processes disrupted have yet to be identified. Important to goal-directed decision-making is one's motivational state, which is used to update the value of actions. As ethanol dependence disrupts decision-making processes, we hypothesized that ethanol dependence could alter sensitivity to motivational state and/or value updating, thereby reducing the capability for adaptive behavior. Here we employed a sequential instrumental learning task to examine this hypothesis. In two experiments, mice underwent chronic intermittent ethanol (CIE) or air (Air) vapor exposure and repeated withdrawal procedures to induce ethanol dependence. Mice were then trained on a sequence of distal and proximal lever pressing for sucrose under either mild or more severe food restriction. Half of all Air and CIE mice then underwent a motivational shift to a less hungry state and effects of this motivational shift were evaluated across three days. First, mice were re-exposed to sucrose, and effects of food restriction state and CIE exposure on lick and consummatory behavior were examined in the absence of lever pressing. Over the next two days, mice underwent a brief non-rewarded test and then a rewarded test where the ability to retrieve and infer sucrose value to guide lever pressing was measured. In the sucrose re-exposure session, prior CIE exposure altered sucrose-seeking in mice with a history of mild but not more severe food restriction, suggesting altered motivational sensitivity. During lever press testing, CIE mice were insensitive to decreases in motivational state and did not reduce proximal lever pressing regardless of food restriction state. Mildly restricted CIE mice, but not severely restricted CIE mice, also did not reduce distal pressing to the same degree as Air mice following a downshift in motivational state. Our findings suggest that ethanol dependence may disrupt motivational processes supporting value updating that are important for decision-making.
功能失调的决策在酒精依赖中已被观察到。然而，尚未确定具体被破坏的潜在过程。目标导向决策的一个重要因素是个体的动机状态，它用于更新行为的价值。由于乙醇依赖会破坏决策过程，我们假设乙醇依赖可能会改变对动机状态和/或价值更新的敏感性，从而降低适应行为的能力。在这里，我们采用了一个连续的工具性学习任务来检验这一假设。在两个实验中，小鼠经历了慢性间歇性乙醇（CIE）或空气（Air）蒸气暴露以及反复的戒断程序，以诱导乙醇依赖。然后，小鼠在轻度或更严重的食物限制下，接受了一系列远端和近端压杆按压以获得蔗糖的训练。一半的 Air 和 CIE 小鼠随后经历了一个动机转变，进入了一个不太饥饿的状态，然后评估了这种动机转变对三天的影响。首先，小鼠重新暴露于蔗糖中，并在没有压杆按压的情况下，检查了食物限制状态和 CIE 暴露对舔舐和摄取行为的影响。在接下来的两天里，小鼠进行了一个短暂的无回报测试，然后进行了一个有回报的测试，在这个测试中，测量了检索和推断蔗糖价值以指导压杆按压的能力。在蔗糖再暴露的过程中，先前的 CIE 暴露改变了轻度食物限制但不是更严重食物限制的小鼠对蔗糖的寻求，这表明了对动机敏感性的改变。在压杆按压测试中，CIE 小鼠对动机状态的降低不敏感，无论食物限制状态如何，它们都不会减少近端压杆按压。轻度限制的 CIE 小鼠，但不是严重限制的 CIE 小鼠，在动机状态下降后，也不会像 Air 小鼠那样，以相同的程度减少远端按压。我们的研究结果表明，乙醇依赖可能会破坏支持价值更新的动机过程，而价值更新对决策很重要。
