Laboratory of Endocrine Physiology, RJ, Brazil.
Neurophysiology Laboratory, Biology Institute, State University of Rio de Janeiro, RJ, Brazil.
Appetite. 2021 May 1;160:105115. doi: 10.1016/j.appet.2021.105115. Epub 2021 Jan 14.
Tobacco smoke during gestation is associated with increased consumption of palatable foods by the offspring in humans and rats. Postpartum relapse is observed in lactating women who quit smoking during pregnancy, putting their children at risk of adverse health outcomes caused by secondhand smoke. Nicotine is transferred through milk and alters the dopaminergic reward system of adult male rats, reducing dopamine action in the nucleus accumbens (NAc) and hypothalamic arcuate nucleus. Here, we evaluated the long-term effects of nicotine-only exposure during lactation on eating behavior, anxiety, locomotion, dopaminergic system, hypothalamic leptin signaling and nicotinic receptor in the adult female rat progeny. Two days after birth (PN2), Wistar rat dams were separated into control and nicotine (Nic) groups for implantation of osmotic minipumps that released respectively saline or 6 mg/kg nicotine. Lactating dams were kept with 6 pups. After weaning (PN21; nicotine withdrawal), only the female offspring were studied. Euthanasia occurred at PN180. Nic females showed hyperphagia, preference for a high-sucrose diet, increased anxiety-like behavior, lower tyrosine hydroxylase (TH), lower dopamine transporter and higher dopamine receptor (Drd2) in NAc; lower Drd1 in prefrontal cortex and lower TH in dorsal striatum (DS). These animals showed changes that can explain their hyperphagia, such as: lower leptin signaling pathway (Lepr, pJAK2, pSTAT3) and Chrna7 expression in hypothalamus. Neonatal nicotine exposure affects the brain reward system of the female progeny differently from males, mainly decreasing dopamine production in NAc and DS. Therefore, Nic females are more susceptible to develop food addiction and obesity.
孕期吸烟会使人类和大鼠的后代增加对美味食物的消费。在怀孕期间戒烟的哺乳期妇女会出现产后复发，使她们的孩子面临二手烟造成的不良健康后果的风险。尼古丁通过乳汁传递，并改变成年雄性大鼠的多巴胺奖赏系统，减少伏隔核（NAc）和下丘脑弓状核中的多巴胺作用。在这里，我们评估了哺乳期仅暴露于尼古丁对成年雌性大鼠后代的进食行为、焦虑、运动、多巴胺系统、下丘脑瘦素信号和烟碱型乙酰胆碱受体的长期影响。出生后两天（PN2），Wistar 大鼠母鼠被分为对照组和尼古丁（Nic）组，用于植入分别释放生理盐水或 6mg/kg 尼古丁的渗透微型泵。哺乳期母鼠与 6 只幼崽在一起。断奶后（PN21；尼古丁戒断），仅研究雌性后代。PN180 时安乐死。Nic 雌性大鼠表现出摄食过度、偏好高蔗糖饮食、焦虑样行为增加、NAc 中的酪氨酸羟化酶（TH）、多巴胺转运蛋白降低和多巴胺受体（Drd2）升高；前额叶皮层中的 Drd1 降低和背侧纹状体（DS）中的 TH 降低。这些动物表现出的变化可以解释它们的摄食过度，例如：下丘脑瘦素信号通路（Lepr、pJAK2、pSTAT3）和 Chrna7 表达降低。新生期尼古丁暴露对雌性后代的大脑奖赏系统的影响与雄性不同，主要是减少 NAc 和 DS 中的多巴胺产生。因此，Nic 雌性更容易发展为食物成瘾和肥胖。
