Downing Chris, Balderrama-Durbin Christina, Hayes Jonathan, Johnson Thomas E, Gilliam David
Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
Alcohol Alcohol. 2009 Jan-Feb;44(1):25-33. doi: 10.1093/alcalc/agn082. Epub 2008 Oct 14.
Prenatal exposure to alcohol can have adverse effects on the developing fetus. Two of the hallmarks of children exposed to alcohol prenatally are attention deficits and hyperactivity. While hyperactivity has been observed in rats following prenatal ethanol exposure, few studies have examined these effects in mice. The present study investigated the effects of prenatal ethanol exposure on activity in mice from three inbred strains: C57BL/6 (B6), Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS).
On Days 7 through 18 of gestation, mice were intragastrically intubated twice daily with either 3.0 g/kg ethanol (E) or an isocaloric amount of maltose-dextrin (MD); non-intubated control (NIC) litters were also generated. Offspring activity was monitored at 30, 60, 90 and 150 days of age.
While results showed no effects of prenatal ethanol exposure on any measures of activity, we did observe differences in baseline activity among the strains. ISS mice were more active than B6 and ILS for all activity measures except stereotypy; B6 mice had higher measures of stereotypy than ILS and ISS. Younger mice were more active than older mice. The only sex effects were on measures of stereotypy, where males had higher scores.
Mice are an excellent organism to study genetic influences on many phenotypes. However, our study and others have shown few effects of prenatal ethanol exposure on behavior in mice. It appears as if the prenatal period in mice, corresponding to organogenesis, is not a sensitive period for producing behavioral deficits following ethanol exposure. It is likely that the first 2 weeks postnatally, corresponding to the brain growth spurt, are more sensitive for producing behavioral effects.
孕期暴露于酒精会对发育中的胎儿产生不良影响。产前暴露于酒精的儿童的两个标志性特征是注意力缺陷和多动。虽然在产前乙醇暴露后的大鼠中观察到了多动情况,但很少有研究在小鼠中检验这些影响。本研究调查了产前乙醇暴露对三种近交系小鼠活动的影响:C57BL/6(B6)、近交长睡眠(ILS)和近交短睡眠(ISS)。
在妊娠第7天至第18天,每天给小鼠经胃插管两次,分别给予3.0 g/kg乙醇(E)或等热量的麦芽糖糊精(MD);还产生了未插管的对照(NIC)窝仔。在子代30、60、90和150日龄时监测其活动情况。
虽然结果显示产前乙醇暴露对任何活动指标均无影响,但我们确实观察到各品系之间在基线活动方面存在差异。除刻板行为外,ISS小鼠在所有活动指标上都比B6和ILS小鼠更活跃;B6小鼠的刻板行为指标高于ILS和ISS小鼠。较年轻的小鼠比年长的小鼠更活跃。唯一的性别效应体现在刻板行为指标上,雄性得分更高。
小鼠是研究遗传对多种表型影响的优良生物体。然而,我们的研究和其他研究表明,产前乙醇暴露对小鼠行为的影响很小。似乎小鼠孕期对应器官发生期,并非乙醇暴露后产生行为缺陷的敏感期。很可能出生后前两周对应脑发育快速期,对产生行为影响更敏感。