Izumi Y, Kitabayashi R, Funatsu M, Izumi M, Yuede C, Hartman R E, Wozniak D F, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Neuroscience. 2005;136(1):269-79. doi: 10.1016/j.neuroscience.2005.07.015. Epub 2005 Sep 21.
To determine factors that contribute to the learning deficits observed in individuals with fetal alcohol syndrome, we examined the effects of early postnatal ethanol exposure on forms of synaptic plasticity thought to underlie memory. Treatment of rat pups with ethanol on postnatal day 7 impaired the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation and abolished homosynaptic long-term depression in the CA1 region of hippocampal slices prepared at postnatal day 30. An N-methyl-D-aspartate receptor-independent form of long-term potentiation induced by very high frequency stimulation could be induced in slices from ethanol-treated rats. Defects in long-term depression correlated with a diminished contribution of ifenprodil-sensitive N-methyl-D-aspartate receptors to synaptic transmission and defects in a spontaneous alternation behavioral task. Rats exposed to ethanol on postnatal day 7 also exhibited diminished sensitivity of synaptic N-methyl-D-aspartate receptors to block by ethanol at postnatal day 30 and decreased behavioral sedation to systemic ethanol injections. These results indicate that changes in synaptic plasticity and N-methyl-D-aspartate receptor function are likely to provide a neural substrate for the cognitive and behavioral changes that follow developmental ethanol exposure.
为了确定导致胎儿酒精综合征个体出现学习缺陷的因素，我们研究了出生后早期乙醇暴露对被认为是记忆基础的突触可塑性形式的影响。在出生后第7天用乙醇处理幼鼠，会损害N-甲基-D-天冬氨酸受体依赖性长时程增强的诱导，并消除出生后第30天制备的海马切片CA1区的同突触长时程抑制。由非常高频刺激诱导的一种不依赖N-甲基-D-天冬氨酸受体的长时程增强形式，可在乙醇处理大鼠的切片中诱导产生。长时程抑制的缺陷与ifenprodil敏感的N-甲基-D-天冬氨酸受体对突触传递的贡献减少以及自发交替行为任务中的缺陷相关。在出生后第7天暴露于乙醇的大鼠，在出生后第30天也表现出突触N-甲基-D-天冬氨酸受体对乙醇阻断的敏感性降低，以及对全身注射乙醇的行为镇静作用减弱。这些结果表明，突触可塑性和N-甲基-D-天冬氨酸受体功能的变化可能为发育过程中乙醇暴露后的认知和行为变化提供神经基础。
