Levin E D, Wilkerson A, Jones J P, Christopher N C, Briggs S J
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res Dev Brain Res. 1996 Dec 23;97(2):207-15. doi: 10.1016/s0165-3806(96)00144-7.
Cigarette smoking during pregnancy has been shown in a variety of studies to be associated with cognitive deficits in the children. Nicotine administration to rats during gestation has been found to cause subtle cognitive effects in the offspring. Some individual differences in cognitive impairment may be related to prenatal nicotine effects on noradrenergic (NE) systems. In the current study, 10 Sprague-Dawley rat dams were infused with approximately 2 mg/kg/day of nicotine ditartrate via osmotic minipumps and 10 control dams were exposed to vehicle-containing minipumps from gestational day (GD) 4-20. Starting on postnatal day (PND) 50, the offspring were tested for T-maze rewarded spatial alternation with intertrial intervals of 0, 10, 20, or 40 s. There was a sex- and delay-dependent effect of prenatal nicotine exposure on T-maze alternation. Nicotine-exposed males showed a significant deficit at the 0 s delay. In radial-arm maze (RAM) acquisition training there were no significant nicotine effects. However, significant nicotine-related effects were seen with subsequent behavioral and pharmacological challenges in the RAM. Changing the RAM testing location to an identical maze in a different room elicited a significant choice accuracy deficit in the prenatal nicotine-exposed rats compared with controls. Acute nicotine challenge did not cause any differential effects in the prenatal nicotine and control groups. During the isoproterenol (beta-NE agonist) challenge phase there appeared a significant facilitation of choice accuracy and speeding of response in the prenatal nicotine exposure group which was not seen in the control group. The alpha-NE agonist phenylpropanolamine caused a significant deficit in control females but not in the females prenatally exposed to nicotine. No differential effects of the alpha-NE antagonist phenoxybenzamine were seen in the prenatal nicotine and control groups. Throughout RAM testing there was a significant sex effect with males having better choice accuracy than females. These results demonstrate that the persisting cognitive effects of prenatal exposure to 2 mg/kg/day cause subtle effects in cognitive performance which can be elicited with behavioral and pharmacological challenge. These results also support previous studies suggesting the involvement of NE systems in persisting effects of prenatal nicotine exposure.
多项研究表明，孕期吸烟与儿童认知缺陷有关。已发现孕期给大鼠注射尼古丁会对其后代产生细微的认知影响。认知障碍的一些个体差异可能与产前尼古丁对去甲肾上腺素能（NE）系统的影响有关。在本研究中，10只斯普拉格-道利大鼠母鼠通过渗透微型泵每天注入约2mg/kg的酒石酸尼古丁，10只对照母鼠在妊娠第4天至第20天暴露于含赋形剂的微型泵。从出生后第50天开始，对后代进行T迷宫奖励空间交替测试，试验间隔为0、10、20或40秒。产前尼古丁暴露对T迷宫交替有性别和延迟依赖性影响。暴露于尼古丁的雄性在0秒延迟时表现出显著缺陷。在放射状臂迷宫（RAM）获取训练中，没有显著的尼古丁效应。然而，在随后的RAM行为和药理学挑战中观察到了显著的尼古丁相关效应。将RAM测试位置改为另一个房间中的相同迷宫，与对照组相比，产前暴露于尼古丁的大鼠出现了显著的选择准确性缺陷。急性尼古丁挑战在产前尼古丁组和对照组中未产生任何差异效应。在异丙肾上腺素（β-NE激动剂）挑战阶段，产前尼古丁暴露组的选择准确性有显著提高，反应速度加快，而对照组未出现这种情况。α-NE激动剂苯丙醇胺在对照雌性大鼠中导致显著缺陷，但在产前暴露于尼古丁的雌性大鼠中未出现。产前尼古丁组和对照组在α-NE拮抗剂酚苄明方面未观察到差异效应。在整个RAM测试中，存在显著的性别效应，雄性的选择准确性优于雌性。这些结果表明，产前每天暴露于2mg/kg尼古丁的持续认知效应会对认知表现产生细微影响，这种影响可通过行为和药理学挑战引发。这些结果也支持了先前的研究，表明NE系统参与了产前尼古丁暴露的持续效应。
