McMurray M S, Williams S K, Jarrett T M, Cox E T, Fay E E, Overstreet D H, Walker C H, Johns J M
The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7096, USA.
Neurotoxicol Teratol. 2008 Nov-Dec;30(6):475-86. doi: 10.1016/j.ntt.2008.07.001. Epub 2008 Jul 11.
Alcohol consumption and smoking during pregnancy is common, despite the known adverse effects of these drugs on fetal development. Though studies on the effects of each drug separately are published, little is known about the effect of concurrent use of alcohol and nicotine in humans or in preclinical models. In this report, we examined the impact of continuous gestational exposure to both ethanol via liquid diet and nicotine via an osmotic minipump on maternal behavior, offspring ethanol intake, and oxytocin levels in a rat model. Dams were tested for the onset of maternal behavior with litters of unexposed surrogate pups and then killed to examine oxytocin levels within specific brain regions. Drug-exposed offspring reared by surrogate dams were tested for ethanol intake at either adolescence or adulthood, and oxytocin levels were measured in relevant brain regions after behavioral tests. Dams exhibited minor deficits in maternal care, which were associated with lower oxytocin levels in both the ventral tegmental and medial preoptic areas compared to control dams. Prenatal exposure altered sex-specific ethanol intake, with differential effects at adolescence and adulthood. Oxytocin system changes were also apparent in the ventral tegmental and medial preoptic regions of drug-exposed adolescent and adult offspring. These results suggest that dam treatment with ethanol and nicotine can somewhat negatively affect the early rearing environment, and that prenatal exposure to both of these drugs results in drinking behavior differing from what would be expected from either drug alone. Oxytocin's possible involvement in the mediation of these effects is highlighted.
尽管已知酒精和烟草对胎儿发育有不良影响，但孕期饮酒和吸烟的情况仍很常见。虽然分别关于每种药物影响的研究已发表，但对于人类或临床前模型中酒精和尼古丁同时使用的影响却知之甚少。在本报告中，我们在大鼠模型中研究了通过液体饮食持续妊娠暴露于乙醇以及通过渗透微型泵暴露于尼古丁对母性行为、后代乙醇摄入量和催产素水平的影响。用未暴露的代孕幼崽测试母鼠的母性行为起始，然后处死母鼠以检查特定脑区的催产素水平。由代孕母鼠抚养的药物暴露后代在青春期或成年期测试乙醇摄入量，并在行为测试后测量相关脑区的催产素水平。与对照母鼠相比，母鼠在母性关怀方面表现出轻微缺陷，这与腹侧被盖区和内侧视前区的催产素水平较低有关。产前暴露改变了性别特异性乙醇摄入量，在青春期和成年期有不同影响。催产素系统变化在药物暴露的青少年和成年后代的腹侧被盖区和内侧视前区也很明显。这些结果表明，用乙醇和尼古丁处理母鼠会对早期饲养环境产生一定的负面影响，并且产前暴露于这两种药物会导致饮酒行为不同于单独使用任何一种药物时的预期情况。突出了催产素可能参与介导这些影响。
