George Mason University, Department of Psychology, 4400 University Drive, Fairfax, VA, 22030, USA.
Neurotoxicol Teratol. 2010 May-Jun;32(3):336-45. doi: 10.1016/j.ntt.2009.12.009. Epub 2010 Jan 7.
Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.
动物模型的产前尼古丁暴露清楚地表明，尼古丁是一种神经致畸物。一些产前尼古丁暴露的持续影响包括低出生体重、行为变化和认知功能缺陷，尽管很少有研究寻找可能贯穿整个生命周期的神经行为和神经化学效应。怀孕的老鼠接受了持续的尼古丁输注（0.96mg/kg/天或 2.0mg/kg/天，游离碱），一直持续到相当于第三个三个月的时期，这是大脑快速发育的时期。由于第三个三个月相当于大鼠的产后期（大约生命的第一周），因此通过母体乳汁向新生幼鼠继续给予尼古丁给药，直到产后第 10 天（P）。在产前和早期产后发育期间暴露于尼古丁会使成年大鼠（P75）在高架十字迷宫（EPM）中产生焦虑样效应，并阻断恐惧条件反射范式中的消退学习，这表明产前和产后尼古丁暴露会影响成年期的焦虑样行为和认知功能。相比之下，尼古丁暴露对青少年动物（P30）在 EPM 中的焦虑样行为没有影响。对烟碱型乙酰胆碱受体的 alpha4、alpha7 和 beta2 亚基的 mRNA 进行分析表明，在产前和产后暴露于尼古丁后，成年海马体和内侧前额叶皮层中这些亚基的表达降低，这表明尼古丁改变了大脑的发育轨迹。这些长期的行为和神经化学变化加强了劝阻怀孕期间吸烟的理由，并清楚地表明，在怀孕期间使用贴片作为戒烟辅助手段并不是一种安全的替代方法。
