Goodlett C R, Peterson S D
Department of Psychology, Indiana University-Purdue University at Indianapolis 46202-3275, USA.
Neurobiol Learn Mem. 1995 Nov;64(3):265-75. doi: 10.1006/nlme.1995.0009.
The two main objectives of this study were (1) to replicate previous findings that 6 days of binge-like exposure to alcohol during the neonatal brain growth spurt induces significant place learning deficits in juvenile rats and (2) to determine whether more limited (3-day) binge-like exposure during the neonatal period induces place learning deficits and whether the effects depend on the developmental timing of the exposure. Using artificial rearing methods and a split-litter experimental design, groups of male and female neonatal rats were given binge-like exposure to 4.5 g/kg/day of ethanol in milk formula either on Postnatal Days (PD) 4-6, PD 7-9, or PD 4-9, which yielded mean peak blood alcohol concentrations of 230-260 mg/dl. Controls included an artificially reared gastrostomy control group (GC) given an isocaloric milk formula diet on PD 4-9 and a suckle control group reared normally by lactating dams. Acquisition of place learning in the Morris spatial navigation task was trained for 6 consecutive days beginning on PD 26; a probe trial was given at the end of the sixth day. As expected, both males and females given alcohol on PD 4-9 had significant deficits in acquisition and probe trial performance relative to SC and GC groups. Males given the PD 7-9 exposure had significant place learning deficits which were as severe as with the full 6-day exposure. The PD 4-6 exposure in males produced only a nonsignificant trend toward slower acquisition. Females were not significantly affected by either 3-day exposure. The latter phase of the neonatal brain growth spurt appears to constitute a sex-specific period of enhanced vulnerability to alcohol-induced developmental spatial learning deficits.
（1）重复先前的研究结果，即在新生大鼠脑发育激增期进行6天的暴饮样酒精暴露会导致幼鼠出现显著的位置学习缺陷；（2）确定在新生儿期进行更有限的（3天）暴饮样暴露是否会导致位置学习缺陷，以及这些影响是否取决于暴露的发育时间。采用人工饲养方法和分窝实验设计，将雄性和雌性新生大鼠分组，在出生后第（PD）4 - 6天、PD 7 - 9天或PD 4 - 9天，以4.5 g/kg/天的乙醇剂量在牛奶配方中给予暴饮样暴露，这导致平均峰值血酒精浓度为230 - 260 mg/dl。对照组包括在PD 4 - 9天给予等热量牛奶配方饮食的人工饲养胃造口对照组（GC）和由哺乳母鼠正常饲养的哺乳对照组。从PD 26开始连续6天训练在莫里斯空间导航任务中获取位置学习；在第六天结束时进行一次探测试验。正如预期的那样，在PD 4 - 9天给予酒精的雄性和雌性大鼠在获取和探测试验表现方面相对于SC和GC组都有显著缺陷。在PD 7 - 9天暴露的雄性大鼠有显著的位置学习缺陷，其严重程度与全6天暴露时相同。雄性大鼠在PD 4 - 6天的暴露仅产生了获取速度减慢的不显著趋势。雌性大鼠在任何一种3天暴露中均未受到显著影响。新生儿脑发育激增的后期似乎构成了一个对酒精诱导的发育性空间学习缺陷易感性增强的性别特异性时期。
