Tobacco exposure during development leads to neurobehavioral dysfunction in children, even when exposure is limited to secondhand smoke. We have previously shown in rats that developmental exposure to tobacco smoke extract (TSE), at levels mimicking secondhand smoke, starting preconception and extending throughout gestation, evoked subsequent locomotor hyperactivity and cognitive impairment. These effects were greater than those caused by equivalent exposures to nicotine alone, implying that other agents in tobacco smoke contributed to the adverse behavioral effects. In the present study, we examined the critical developmental windows of vulnerability for these effects, restricting TSE administration (0.2 mg/kg/day nicotine equivalent, or DMSO vehicle, delivered by subcutaneously-implanted pumps) to three distinct 10 day periods: the 10 days preceding mating, the first 10 days of gestation (early gestation), or the second 10 days of gestation (late gestation). The principal behavioral effects revealed a critical developmental window of vulnerability, as well as sex selectivity. Late gestational TSE exposure significantly increased errors in the initial training on the radial-arm maze in female offspring, whereas no effects were seen in males exposed during late gestation, or with either sex in the other exposure windows. In attentional testing with the visual signal detection test, male offspring exposed to TSE during early or late gestation showed hypervigilance during low-motivating conditions. These results demonstrate that gestational TSE exposure causes persistent behavioral effects that are dependent on the developmental window in which exposure occurs. The fact that effects were seen at TSE levels modeling secondhand smoke, emphasizes the need for decreasing involuntary tobacco smoke exposure, particularly during pregnancy.

在发育过程中接触烟草会导致儿童神经行为功能障碍，即使接触仅限于二手烟也是如此。我们先前已经在大鼠中发现，暴露于烟草烟雾提取物（TSE）的发育水平类似于二手烟，开始受孕并一直延伸到整个妊娠期，引起了随后的运动过度活跃和认知障碍。这些影响大于仅单独接触尼古丁所引起的影响，这意味着烟草烟雾中的其他物质也对不良行为产生了影响。在本研究中，我们检查了这些影响的脆弱性的关键发展窗口，将TSE给药（皮下植入泵输送的0.2 mg / kg /天尼古丁当量或DMSO媒介物）限制在三个不同的10天周期内：交配前10天，妊娠的前10天（早期妊娠）或妊娠的第二10天（晚期妊娠）。主要的行为影响揭示了脆弱性和性别选择性的关键发展窗口。妊娠后期TSE暴露显着增加了雌性后代在the臂迷宫的初始训练中的错误，而在妊娠后期暴露的雄性中或在其他暴露窗口中的任何性别均未观察到影响。在视觉信号检测测试的注意力测试中，在妊娠早期或晚期暴露于TSE的雄性后代在低动力条件下表现出过度警惕。这些结果表明，妊娠TSE暴露会引起持续的行为影响，这取决于发生暴露的发育窗口。