Jang Minji, Jung Taesub, Kim Woonhee, Kim Inyong, Jeong Yoonhwa, Noh Jihyun
Department of Science Education, College of Education, Dankook University, Yongin-si, Gyeonggi-do.
Department of Food Science and Nutrition and Research Center for Industrialization of Natural Nutraceuticals, Dankook University, Cheonan-si, Chungnam, Republic of Korea.
Behav Pharmacol. 2020 Feb;31(1):34-44. doi: 10.1097/FBP.0000000000000504.
Nicotine replacement therapy (NRT) has been developed as a drug therapy for smoking cessation and has been considered a safe alternative to smoking during pregnancy. However, the effects of long-term nicotine exposure via NRT on the fetus are still being debated. Here, we determined the effects of long-term maternal nicotine exposure in gestation and lactation on nicotine-related behavior and drug vulnerability in dams and offspring rats. To expose long-term nicotine, on gestation day 14, pregnant rats were implanted with osmotic minipumps releasing nicotine tartrate (6 mg/kg/day, subcutaneously, equivalent to 2 mg nicotine-freebase) for 28 days. The concentration of cotinine in blood was 373.0 ± 109.0 ng/ml in dams and 12.50 ± 1.19 ng/ml in offspring rats. In dams, we found no significant differences in anxiety-like behaviors and various maternal behaviors such as touching, sniffing, pup licking, laying on pups, and retrieval between saline- and nicotine-exposed groups. Adolescent offspring female rats showed no significant differences in anxiety-like behavior and forced alcohol consumption between saline- and nicotine-exposed groups. Nicotine-exposed offspring rats showed more increased nicotine aversion than saline-exposed groups, but the effect was disturbed in the forced alcohol consumption condition on the first day of the nicotine consumption test. Taken together, these results suggest that, in the last gestation and lactation period corresponding to the second and third trimester of human pregnancy, long-term maternal nicotine exposure has a minor effect on dam and female offspring health and does not involve serious pathological changes in rat offspring, despite the presence of nicotine in their blood.
尼古丁替代疗法（NRT）已被开发用作戒烟的药物疗法，并被认为是孕期吸烟的一种安全替代方法。然而，通过NRT长期接触尼古丁对胎儿的影响仍存在争议。在此，我们确定了孕期和哺乳期母体长期接触尼古丁对母鼠及其后代大鼠与尼古丁相关行为和药物易感性的影响。为了使母鼠长期接触尼古丁，在妊娠第14天，给怀孕大鼠植入渗透微型泵，皮下注射释放酒石酸尼古丁（6毫克/千克/天，相当于2毫克游离碱尼古丁），持续28天。母鼠血液中可替宁浓度为373.0±109.0纳克/毫升，后代大鼠为12.50±1.19纳克/毫升。在母鼠中，我们发现生理盐水组和尼古丁暴露组在焦虑样行为以及各种母性行为（如触摸、嗅闻、舔舐幼崽、趴在幼崽身上和找回幼崽）方面没有显著差异。青春期雌性后代大鼠在生理盐水组和尼古丁暴露组之间的焦虑样行为和强迫饮酒量方面没有显著差异。尼古丁暴露的后代大鼠比生理盐水暴露组表现出更多的尼古丁厌恶增加，但在尼古丁消费测试第一天的强迫饮酒条件下，这种影响受到干扰。综上所述，这些结果表明，在相当于人类妊娠第二和第三孕期的最后孕期和哺乳期，母体长期接触尼古丁对母鼠和雌性后代健康的影响较小，并且尽管后代大鼠血液中存在尼古丁，但并不涉及严重的病理变化。
