Department of Biomedical and Molecular Sciences, Pharmacology and Toxicology Graduate Program, Queen's University, Kingston, ON K7L 3N6, Canada.
Behav Brain Res. 2012 Jul 15;233(1):162-8. doi: 10.1016/j.bbr.2012.04.042. Epub 2012 Apr 27.
Ethanol consumption during pregnancy can produce a variety of teratogenic effects in offspring, termed Fetal Alcohol Spectrum Disorders (FASD). The most debilitating and permanent consequence of chronic prenatal ethanol exposure (CPEE) is neurobehavioral teratogenicity, which often manifests as cognitive and behavioral impairments, including deficits in spatial learning and memory. This study tested the hypothesis that a modified dry-land version of the multi-choice Biel-maze task is more sensitive than the rewarded-alternation Y-maze task for the determination of spatial learning and memory deficits of ethanol teratogenicity. Pregnant guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (control) for 5days/week throughout gestation. CPEE resulted in ethanol neurobehavioral teratogenicity in offspring, as demonstrated by increased spontaneous locomotor activity at postnatal day (PD) 10 and decreased brain weight at euthanasia (PD 150-200). On PD 21, offspring were randomly assigned to one of two tasks to assess spatial learning and memory performance: a dry-land version of the Biel maze or a rewarded-alternation Y-maze. Animals were habituated to the environment of their assigned task and performance of each CPEE or control offspring was measured. In the modified Biel maze, CPEE and control offspring were not different for percent completed trials or time to complete a trial. However, CPEE offspring made more errors (reversals and entering dead ends) in the Biel maze, demonstrating impaired spatial learning and memory. In contrast, CPEE offspring did not have impaired performance of the rewarded-alternation Y-maze task. Therefore, the modified dry-land version of the Biel-maze task, which measures cognitive performance using a complex multi-choice design, is more sensitive in demonstrating CPEE-induced spatial learning and memory deficits compared with a simple, rewarded-alternation Y-maze task.
孕期乙醇摄入可导致后代出现多种致畸效应,称为胎儿酒精谱系障碍(Fetal Alcohol Spectrum Disorders,FASD)。慢性产前乙醇暴露(Chronic Prenatal Ethanol Exposure,CPEE)最具致残性和永久性的后果是神经行为致畸性,常表现为认知和行为障碍,包括空间学习和记忆缺陷。本研究旨在验证以下假设:改良的多选 Biel 迷宫任务的旱地版本比奖励交替 Y 迷宫任务更能灵敏地测定乙醇致畸性的空间学习和记忆缺陷。妊娠豚鼠每周 5 天接受 4g/kg 母体体重的乙醇或等热量蔗糖/配对喂养(对照)。CPEE 导致后代出现乙醇神经行为致畸性,表现在产后第 10 天自发运动活动增加,安乐死时脑重减少(产后 150-200 天)。产后第 21 天,将幼仔随机分配到两项任务之一,以评估空间学习和记忆表现:改良的 Biel 迷宫或奖励交替 Y 迷宫。使动物适应其指定任务的环境,并测量每个 CPEE 或对照幼仔的表现。在改良的 Biel 迷宫中,CPEE 和对照幼仔在完成试验的百分比或完成试验的时间上没有差异。然而,CPEE 幼仔在 Biel 迷宫中犯的错误更多(逆转和进入死胡同),表明空间学习和记忆受损。相比之下,CPEE 幼仔在奖励交替 Y 迷宫任务中没有表现出受损的表现。因此,改良的 Biel 迷宫旱地版本,通过复杂的多选设计测量认知表现,比简单的奖励交替 Y 迷宫任务更灵敏地显示 CPEE 诱导的空间学习和记忆缺陷。