Thomas J D, Melcer T, Weinert S, Riley E P
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA, USA.
Alcohol. 1998 Oct;16(3):237-42. doi: 10.1016/s0741-8329(98)00008-1.
Children of women who consume high amounts of alcohol during their pregnancies vary greatly in physical and behavioral outcomes. Although many factors, such as dose and timing of exposure, undoubtedly contribute to this variation, one important determinant may be genetic differences in the response to alcohol. The present study examined activity levels in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats following neonatal alcohol exposure. These lines were selectively bred for extremes in ethanol-induced "sleep times." The HAS and LAS offspring were exposed to alcohol via an artificial rearing procedure using the "pup-in-the-cup" technique. Rat pups were exposed to ethanol (6 g/kg/day) from postnatal day (PD) 4 through 7 and faded to a dose of 3 g/kg/day on PD 8 and 9. An artificially reared gastrostomy control group (GC) and a normally reared suckle control group (SC) were also included. Activity level was measured on PD 18 through PD 21 for 30 min daily in automated activity monitors. Neonatal ethanol exposure produced overactivity in HAS rats, relative to their controls, but the same ethanol treatment had no effect on the LAS rats. Importantly, there were no differences in blood alcohol concentrations (around 420 mg/dl) between the two lines during the treatment period. These data suggest that genetic differences in response to alcohol may be a predictor for some of the behavioral teratogenic effects of alcohol.
孕期大量饮酒的女性所生子女在身体和行为方面的结果差异很大。尽管许多因素,如接触酒精的剂量和时间,无疑导致了这种差异,但一个重要的决定因素可能是对酒精反应的基因差异。本研究检测了新生期酒精暴露后高酒精敏感性(HAS)和低酒精敏感性(LAS)大鼠的活动水平。这些品系是通过选择性培育获得的,在乙醇诱导的“睡眠时间”方面表现出极端差异。通过使用“杯中小鼠”技术的人工饲养程序,让HAS和LAS后代接触酒精。从出生后第4天(PD)到第7天,给幼鼠喂食乙醇(6 g/kg/天),在第8天和第9天逐渐减至3 g/kg/天的剂量。还设置了一个人工饲养的胃造口术对照组(GC)和一个正常饲养的哺乳对照组(SC)。在出生后第18天至第21天,每天在自动活动监测仪中测量30分钟的活动水平。相对于对照组,新生期乙醇暴露使HAS大鼠出现活动过度,但相同的乙醇处理对LAS大鼠没有影响。重要的是,在治疗期间,两品系之间的血液酒精浓度(约420 mg/dl)没有差异。这些数据表明,对酒精反应的基因差异可能是酒精某些行为致畸作用的一个预测指标。