Sakata-Haga Hiromi, Dominguez Hector D, Sei Hiroyoshi, Fukui Yoshihiro, Riley Edward P, Thomas Jennifer D
Department of Psychology, Center for Behavioral Teratology, San Diego State University, San Diego, California 92120, USA.
Alcohol Clin Exp Res. 2006 May;30(5):899-907. doi: 10.1111/j.1530-0277.2006.00105.x.
Disruptions in sleep and feeding rhythms are among the consequences of prenatal alcohol exposure. Previously, we reported that ethanol exposure during the second trimester equivalent in rats produces long-lasting impairments in circadian system functioning. In the present study, we examined the effects of ethanol exposure during the third trimester equivalent brain growth spurt on the development of the circadian clock system.
Sprague-Dawley male rat pups were exposed to 6.0 g/kg/d ethanol via an artificial rearing procedure on postnatal days (PD) 4 through 9 (EtOH). An artificially reared gastrostomized control group and a normally reared suckle control group were also included. At 10 to 12 weeks of age, wheel-running behavior was measured continuously under a 12-hour/12-hour light/dark (LD) cycle. Thereafter, subjects were exposed to a 6-hour phase delay of the LD cycle, and the ability to adjust to the new LD cycle was evaluated.
Before the phase delay, onset time of activity and acrophases of activity in all 3 groups were not significantly different from one another. After the 6-hour LD cycle delay, EtOH subjects were slower to adapt to the new cycle compared with both control groups, as measured by both activity onset and acrophase. Throughout the experiment, activity levels of EtOH subjects tended to be higher compared to both controls.
These data demonstrate that ethanol exposure during the third trimester disrupts the ability to synchronize circadian rhythm to light cues. Disruptions in circadian regulation may cause abnormal behavioral rhythmicity, such as disrupted sleep and feeding patterns, as seen in individuals prenatally exposed to ethanol.
睡眠和进食节律紊乱是产前酒精暴露的后果之一。此前,我们报道大鼠孕期中期同等剂量的乙醇暴露会导致昼夜节律系统功能出现长期损害。在本研究中,我们研究了孕期晚期同等剂量乙醇暴露对生物钟系统发育的影响,此阶段相当于大脑发育的快速期。
通过人工饲养程序,在出生后第4至9天(PD4 - 9)给斯普拉格 - 道利雄性幼鼠暴露于6.0 g/kg/d的乙醇(EtOH组)。还包括一个人工饲养的胃造口对照组和一个正常饲养的哺乳对照组。在10至12周龄时,在12小时/12小时光照/黑暗(LD)周期下连续测量转轮行为。此后,使受试者暴露于LD周期6小时的相位延迟,并评估其适应新LD周期的能力。
在相位延迟前,所有3组的活动开始时间和活动高峰期彼此之间无显著差异。在LD周期延迟6小时后,通过活动开始时间和高峰期测量,与两个对照组相比,EtOH组的受试者适应新周期的速度较慢。在整个实验过程中,EtOH组受试者的活动水平相较于两个对照组往往更高。
这些数据表明,孕期晚期的乙醇暴露会破坏昼夜节律与光照信号同步的能力。昼夜节律调节的破坏可能会导致异常的行为节律,如睡眠和进食模式紊乱,这在产前暴露于乙醇的个体中可见。