Chandler Cassie M, Follett Meagan E, Porter Nicholas J, Liang Kevin Y, Vallender Eric J, Miller Gregory M, Rowlett James K, Platt Donna M
Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Department of Psychiatry & Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Alcohol. 2017 Sep;63:19-26. doi: 10.1016/j.alcohol.2017.03.002. Epub 2017 Jun 23.
Humans with histories of prolonged heavy alcohol use exhibit poorer performance on cognitive tasks associated with problem solving, short-term memory, and visuospatial reasoning, even following the cessation of drinking, when compared with healthy controls. It is unclear, however, whether the cognitive problems are a consequence of alcohol exposure or a contributing factor to alcohol-use disorders. Here, we examined the relationship between performance on a novel object recognition (NOR) task and total alcohol consumption (TAC) in adult male rhesus macaques (n = 12; ETH group; trained to self-administer alcohol). NOR performance in this group was assessed prior to induction of alcohol drinking ("pre") and, again, after a 1-year abstinence period ("post") and was compared to the performance of a second group (n = 6; Control group), which was alcohol-naïve. In the NOR task, difficulty was manipulated across three phases by varying specific object features and/or by varying duration of access to objects. For each monkey, we measured aspects of novelty-related behavior including novelty detection, novelty reactivity, and perseverative behavior. TAC during induction and a "free" access period in which the monkey could choose between water and a 4% w/v ethanol solution also was determined. We found that performance deficits in the NOR task were a consequence of high total alcohol intake instead of a predictor of subsequent high intake. Poor NOR performance in drinkers with the highest intakes was characterized by increased perseverative behavior rather than an inability to detect or react to novelty. Finally, the observed deficits are long-lasting - persisting even after a year of abstinence. Given the prevalent and persistent nature of alcohol-induced cognitive deficits in patients in treatment settings, understanding the nature of the deficit and its neural basis could ultimately offer novel treatment approaches based on the reversal of alcohol-induced impairment.
与健康对照组相比，有长期大量饮酒史的人在与解决问题、短期记忆和视觉空间推理相关的认知任务上表现较差，即使在戒酒之后也是如此。然而，尚不清楚认知问题是酒精暴露的结果还是酒精使用障碍的一个促成因素。在这里，我们研究了成年雄性恒河猴（n = 12；乙醇组；经训练可自行摄入酒精）在新物体识别（NOR）任务中的表现与总酒精摄入量（TAC）之间的关系。在诱导饮酒之前（“pre”）以及在1年的禁欲期之后（“post”）评估该组的NOR表现，并将其与第二组（n = 6；对照组）的表现进行比较，第二组未接触过酒精。在NOR任务中，通过改变特定物体特征和/或改变接触物体的持续时间，在三个阶段操纵难度。对于每只猴子，我们测量了与新奇相关行为的各个方面，包括新奇检测、新奇反应性和持续性行为。还确定了诱导期间和猴子可以在水和4% w/v乙醇溶液之间进行选择的“自由”获取期内的TAC。我们发现，NOR任务中的表现缺陷是高总酒精摄入量的结果，而不是随后高摄入量的预测因素。摄入量最高的饮酒者NOR表现不佳的特征是持续性行为增加，而不是无法检测新奇事物或对新奇事物做出反应。最后，观察到的缺陷是持久的——即使在禁欲一年后仍持续存在。鉴于治疗环境中患者酒精诱导的认知缺陷普遍且持续存在，了解缺陷的性质及其神经基础最终可能会基于逆转酒精诱导的损伤提供新的治疗方法。
