Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN, USA.
Addict Biol. 2021 Sep;26(5):e13004. doi: 10.1111/adb.13004. Epub 2021 Jan 28.
Alcohol use disorder (AUD) is characterized by impairments in decision-making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision-making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre-existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set-shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision-making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables-in this case, impaired cognitive flexibility and heightened urgency, respectively-may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.
酒精使用障碍（AUD）的特征是决策受损，这种受损既可以表现为稳定的特征，也可以表现为短暂的状态。认知灵活性反映了无法更新指导决策的信息，据认为这导致了无法戒酒。虽然有几项研究报告了慢性酒精暴露后认知灵活性受损的证据，但先前存在的认知灵活性受损是 AUD 的遗传风险因素的证据却很少。在这里，我们发现，在专门用于过度饮酒的（酒精偏好（P）大鼠）动物中，在注意定势转移任务（ASST）上认知灵活性受损。此外，损伤的程度可以预测未来的乙醇消耗，因此表明认知灵活性是一种稳定的特征，能够使人容易饮酒。在第二组实验中，我们观察到 P 大鼠在简单辨别任务中使用先前学习的规则来指导觅食的能力受损。几个行为测量指标的收敛表明，这种损伤反映了一种高度紧急的状态，干扰了决策。在有饮酒史的 Wistar 大鼠中也观察到了类似的简单辨别任务损伤。这些发现表明了特质和状态变量（在这种情况下，分别是认知灵活性受损和紧急程度增加）如何影响过度饮酒的风险。此外，我们的结果表明，认知灵活性和紧迫性既可以作为酒精暴露的风险因素，也可以作为酒精暴露的结果。
