Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada; Department of Biology, University of Victoria, Victoria, British Columbia, Canada.
Alcohol Clin Exp Res. 2014 Jan;38(1):135-43. doi: 10.1111/acer.12227. Epub 2013 Aug 5.
Prenatal ethanol (EtOH) exposure results in a spectrum of structural, cognitive, and behavioral abnormalities, collectively termed "fetal alcohol spectrum disorders" (FASDs). The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of EtOH. Prenatal EtOH exposure can lead to long-lasting impairments in the ability to process spatial information, as well as produce long-lasting deficits in the ability of animals to exhibit long-term potentiation (LTP), a biological model of learning and memory processing. These deficits also have the ability to facilitate EtOH and/or other drug abuse later in life. This study sought to determine prenatal EtOH exposure altered the effects of acute EtOH application on synaptic plasticity.
Prenatal EtOH exposure was modeled using a liquid diet where dams were given 1 of 3 diets: (i) a liquid diet containing EtOH (35.5% EtOH-derived calories), (ii) a liquid diet, isocaloric to the EtOH diet, but with maltose-dextrin substituting for the EtOH-derived calories, and (iii) an ad libitum diet of standard rat chow. Extracellular recordings from transverse brain slices (350 μm) prepared from 50- to 70-day-old rats, following prenatal EtOH exposure (gestational day 1 to 21). LTP was examined in the dentate gyrus following acute EtOH exposure (0, 20, or 50 mM) in these slices.
Prenatal EtOH exposure attenuated LTP in the adult dentate gyrus. In control offspring, acute application of EtOH in adulthood attenuated (20 mM) or blocked (50 mM) LTP. Conversely, the effect of acute EtOH application on LTP was not as pronounced in prenatal EtOH offspring.
Prenatal EtOH exposure alters the sensitivity of the adult dentate gyrus to acute EtOH application producing a long-lasting tolerance to the inhibitory effects of EtOH. This decreased sensitivity may provide a mechanism promoting the formation of drug-associated memories and help explain the increased likelihood of developing an alcohol dependency often observed in individuals with FASDs.
产前乙醇（EtOH）暴露会导致一系列结构、认知和行为异常，统称为“胎儿酒精谱系障碍”（FASD）。海马结构是与学习和记忆密切相关的大脑区域，特别容易受到 EtOH 的致畸作用的影响。产前 EtOH 暴露可导致处理空间信息的能力持久受损，并导致动物表现出长期增强（LTP）的能力持久丧失，LTP 是学习和记忆处理的生物学模型。这些缺陷还有能力促进动物在以后的生活中滥用乙醇和/或其他药物。本研究旨在确定产前 EtOH 暴露改变了急性 EtOH 应用对突触可塑性的影响。
使用液体饮食模型进行产前 EtOH 暴露，其中母鼠接受以下 3 种饮食之一：（i）含有 EtOH（35.5% EtOH 衍生卡路里）的液体饮食，（ii）与 EtOH 饮食等热量但用麦芽糖糊精代替 EtOH 衍生卡路里的液体饮食，以及（iii）自由进食标准大鼠饲料。从产前 EtOH 暴露（妊娠第 1 天至第 21 天）后的 50 至 70 天大鼠制备的横切脑片（350 μm）中进行细胞外记录。在这些切片中，急性 EtOH 暴露（0、20 或 50 mM）后检查齿状回中的 LTP。
产前 EtOH 暴露可减弱成年齿状回中的 LTP。在对照后代中，急性 EtOH 在成年期的应用减弱（20 mM）或阻断（50 mM）LTP。相反，急性 EtOH 应用对 LTP 的影响在产前 EtOH 后代中并不那么明显。
产前 EtOH 暴露改变了成年齿状回对急性 EtOH 应用的敏感性，导致对 EtOH 的抑制作用产生持久的耐受性。这种敏感性降低可能为形成与药物相关的记忆提供了一种机制，并有助于解释在 FASD 患者中经常观察到的发展酒精依赖的可能性增加。
