Hunt Pamela S, Jacobson Sarah E, Torok Elena J
Department of Psychology, College of William and Mary, Williamsburg, VA 23187-8795, USA.
Alcohol. 2009 Sep;43(6):465-74. doi: 10.1016/j.alcohol.2009.08.004.
In humans, prenatal alcohol exposure can result in significant impairments in several types of learning and memory, including declarative and spatial memory. Animal models have been useful for confirming that many of the observed effects are the result of alcohol exposure, and not secondary to poor maternal nutrition or adverse home environments. Wagner and Hunt (2006) reported that rats exposed to ethanol during the neonatal period (postnatal days [PDs] 4-9) exhibited impaired trace fear conditioning when trained as adolescents, but were unaffected in delay fear conditioning. The present series of three experiments represent a more detailed analysis of ethanol-induced deficits in trace conditioning. In Experiment 1, the dose of ethanol given to neonates was varied (3.0, 4.0, or 5.0g/kg/day). There was a dose-dependent reduction in trace conditioning, with the poorest performance observed in animals treated with the highest dose. In Experiment 2, it was found that the impairment in trace conditioning resulting from neonatal ethanol exposure was dependent on the duration of the trace interval used for training; less learning was evident in ethanol-exposed animals trained with longer trace interval durations. These results confirm other reports of delay-dependent memory deficits. Finally, Experiment 3 determined that ethanol exposure limited to the first half of the neonatal period (PDs 4-6) was more detrimental to later trace conditioning than exposure during the second half (PDs 7-9). These results support the hypothesis that trace-conditioning impairments resulting from early ethanol exposure are due to the drug's teratogenic effects on the developing hippocampus, as the findings parallel those observed in animals with discrete hippocampal lesions. Comparisons between delay and trace fear-conditioning performance in animals exposed to ethanol during the brain growth spurt provide a model system to study both selective learning impairments and possible treatment approaches for humans with fetal alcohol spectrum disorders.
在人类中，孕期酒精暴露会导致多种类型的学习和记忆出现显著损害，包括陈述性记忆和空间记忆。动物模型有助于证实许多观察到的影响是酒精暴露的结果，而非继发于母体营养不良或不良家庭环境。瓦格纳和亨特（2006年）报告称，新生期（出生后第4 - 9天）暴露于乙醇的大鼠在青春期接受训练时，表现出痕迹恐惧条件反射受损，但在延迟恐惧条件反射中未受影响。本系列的三个实验对乙醇诱导的痕迹条件反射缺陷进行了更详细的分析。在实验1中，给新生大鼠的乙醇剂量有所不同（3.0、4.0或5.0克/千克/天）。痕迹条件反射存在剂量依赖性降低，接受最高剂量处理的动物表现最差。在实验2中，发现新生期乙醇暴露导致的痕迹条件反射受损取决于用于训练的痕迹间隔时长；在接受较长痕迹间隔时长训练的乙醇暴露动物中，学习效果较差。这些结果证实了其他关于延迟依赖性记忆缺陷的报告。最后，实验3确定，仅限于新生期上半叶（出生后第4 - 6天）的乙醇暴露对后期痕迹条件反射的损害比下半叶（出生后第7 - 9天）的暴露更大。这些结果支持了这样一种假说，即早期乙醇暴露导致的痕迹条件反射损害是由于该药物对发育中的海马体产生致畸作用，因为这些发现与在有离散海马体损伤的动物中观察到的结果相似。对脑发育快速期暴露于乙醇的动物的延迟和痕迹恐惧条件反射表现进行比较，提供了一个模型系统，用于研究选择性学习障碍以及针对患有胎儿酒精谱系障碍的人类的可能治疗方法。
