Paulson R B, Shanfeld J, Vorhees C V, Sweazy A, Gagni S, Smith A R, Paulson J O
Department of Oral Biology, College of Dentistry, Ohio State University, Columbus 43210-1241.
Neurotoxicol Teratol. 1993 May-Jun;15(3):183-92. doi: 10.1016/0892-0362(93)90014-f.
Two dosages of Smokeless Tobacco (ST) extract were given to gravid Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The low dosage contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), and the high dosage contained ST extract equivalent to 4.0 mg/kg nicotine (STD-2). Dams were dosed three times daily at 8 a.m., 11 a.m., and 2 p.m., thus providing total daily nicotine equivalent dosages of 4 mg/kg/day and 12 mg/kg/day. Controls received equivalent amounts of distilled water by gavage. Dams were allowed to deliver and all experimental pups were fostered to control mothers. On postnatal day 1 (PND 1) litters were culled to 4 +/- 1 females and 4 +/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-weaning periods. Behavioral tests included: surface righting, negative geotaxis, swimming development, open-field activity, active avoidance in shuttle box, and Cincinnati swimming maze. Our results show that the STD-2 dose resulted in reduced maternal weight gain. Offspring weights were reduced in a dose-related manner, with the most consistent weight deficits seen in the STD-2 group until PND29. Consistent STD-1 weight deficits were seen up to PND 8. The incidence of deaths was increased in the STD-2 dosage group. No significant treatment-related differences were observed in development of physical landmarks. Male STD-2 pups righted faster than controls, and significant differences were noted in swimming development with the STD-1 group of pups performing less effectively than controls. Activity levels, assessed during both pre- and post-weaning periods were not affected. No treatment-related differences were seen in the active avoidance shuttle box or Cincinnati swimming maze tests, which assessed learning. Female brain weights were reduced in the STD-1 treatment group.
在妊娠第6至20天，通过口服灌胃法给妊娠的斯普拉格-道利大鼠给予两种剂量的无烟烟草（ST）提取物。低剂量组所含的ST提取物相当于1.33毫克/千克尼古丁（STD - 1），高剂量组所含的ST提取物相当于4.0毫克/千克尼古丁（STD - 2）。母鼠每天于上午8点、11点和下午2点给药三次，这样每天给予的尼古丁当量总剂量分别为4毫克/千克/天和12毫克/千克/天。对照组通过灌胃给予等量的蒸馏水。母鼠分娩后，所有实验幼崽都寄养给对照母鼠。在出生后第1天（PND 1），将每窝幼崽挑选至4±1只雌性和4±1只雄性。在断奶前和断奶后的时期监测幼崽的体重、身体标志性发育和行为表现。行为测试包括：表面翻正、负趋地性、游泳发育、旷场活动、穿梭箱主动回避以及辛辛那提游泳迷宫测试。我们的结果表明，STD - 2剂量导致母鼠体重增加减少。后代体重以剂量相关的方式降低，直到PND29，STD - 2组中体重不足最为一致。直到PND 8，STD - 1组体重持续出现不足。STD - 2剂量组的死亡发生率增加。在身体标志性发育方面未观察到与治疗相关的显著差异。雄性STD - 2幼崽比对照组更快翻正，并且在游泳发育方面观察到显著差异，STD - 1组幼崽的表现不如对照组有效。在断奶前和断奶后时期评估的活动水平均未受影响。在评估学习能力的主动回避穿梭箱或辛辛那提游泳迷宫测试中未观察到与治疗相关的差异。STD - 1治疗组雌性幼崽的脑重降低。
