Pauly James R, Sparks Jae A, Hauser Kurt F, Pauly Thomas H
Department of Pharmaceutical Sciences, Chandler College of Medicine, University of Kentucky, Lexington, KY 40636-0082, USA.
Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):329-37. doi: 10.1016/j.ijdevneu.2004.05.009.
Maternal cigarette smoking during pregnancy can result in a wide variety of adverse fetal outcomes, ranging from preterm delivery and low birth weight, to sudden infant death syndrome. In addition, in utero tobacco smoke exposure is associated with delayed or impaired neuropsychological development. Although the causative agent in tobacco smoke that leads to these aberrations is not known, some studies have concluded that nicotine may play an important role. Many studies using animal models of prenatal nicotine exposure have supported the hypothesis that nicotine may directly and/or indirectly cause impairments in fetal and neonatal development. However, in many of the animal studies nicotine has been administered acutely to naive dams, which could lead to significant fetal hypoxia; some routes of drug administration are also very stressful to pregnant dams, and changes in stress hormones could also create an unfavorable fetal environment. In this study, pregnant mice were exposed to chronic nicotine via the drinking solution; locomotor activity and sensitivity to nicotine were evaluated in the offspring. We have previously shown that oral nicotine administration produces behavioral and physiological changes that resemble those seen following other routes of nicotine administration. Although oral nicotine exposure did not significantly alter any aspect of the pregnancy, dams drinking a nicotine-containing solution consumed approximately 20% less volume, compared to saccharin controls. All animals were cross fostered to nicotine naïve lactating dams, immediately after birth. On PN40 and PN60, male mice exposed to in utero nicotine demonstrated significant locomotor hyperactivity in an open filed arena. Although female animals did not show any signs of hyperactivity, they did have a significant attenuation of their hypothermic response to acute nicotine challenge. These results suggest that oral nicotine delivery to pregnant mice causes persistent, gender-dependant changes in behavior and sensitivity to nicotine. This model may be very useful for future studies that try to more accurately define the windows of sensitivity for nicotine exposure and the possible underlying neurochemical mechanisms involved.
孕期母亲吸烟会导致多种不良胎儿结局，从早产和低出生体重到婴儿猝死综合征。此外，子宫内接触烟草烟雾与神经心理发育延迟或受损有关。尽管导致这些异常的烟草烟雾中的致病因子尚不清楚，但一些研究得出结论，尼古丁可能起重要作用。许多使用产前尼古丁暴露动物模型的研究支持了尼古丁可能直接和/或间接导致胎儿和新生儿发育受损的假说。然而，在许多动物研究中，尼古丁是急性给予未接触过的母鼠，这可能导致严重的胎儿缺氧；一些给药途径对怀孕母鼠也极具压力，应激激素的变化也可能营造不利的胎儿环境。在本研究中，怀孕小鼠通过饮用溶液接触慢性尼古丁；对后代的运动活动和对尼古丁的敏感性进行了评估。我们之前已经表明，口服尼古丁会产生行为和生理变化，类似于通过其他尼古丁给药途径所观察到的变化。尽管口服尼古丁暴露并未显著改变怀孕的任何方面，但与糖精对照组相比，饮用含尼古丁溶液的母鼠饮水量减少了约20%。所有动物在出生后立即被交叉寄养给未接触过尼古丁的泌乳母鼠。在出生后第40天和第60天，子宫内接触尼古丁的雄性小鼠在旷场实验中表现出显著的运动活动亢进。尽管雌性动物没有表现出任何多动迹象，但它们对急性尼古丁挑战的体温过低反应明显减弱。这些结果表明向怀孕小鼠口服尼古丁会导致行为和对尼古丁敏感性的持续、性别依赖性变化。该模型可能对未来试图更准确界定尼古丁暴露敏感性窗口以及所涉及的潜在神经化学机制的研究非常有用。
