Levin Edward D, Lawrence Susan, Petro Ann, Horton Kofi, Seidler Frederic J, Slotkin Theodore A
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Pharmacol Biochem Behav. 2006 Nov;85(3):669-74. doi: 10.1016/j.pbb.2006.11.006. Epub 2006 Dec 28.
There is a significant association between maternal cigarette smoking during pregnancy and greater subsequent risk of smoking in female offspring. In animal models, prenatal nicotine exposure causes persistent alterations in cholinergic and monoaminergic systems, both of which are important for nicotine actions underlying tobacco addiction. Accordingly, the current study was conducted to determine if there is a cause-and-effect relationship between prenatal nicotine exposure and nicotine self-administration starting in adolescence. Pregnant rats were administered nicotine (6 mg/kg/day) by osmotic minipump infusion throughout gestation and then, beginning in adolescence and continuing into adulthood, female offspring were given access to nicotine via a standard operant IV self-administration procedure (0.03 mg/kg/infusion). Gestational nicotine exposure did not alter the initial rate of nicotine self-administration. However, when animals underwent one week of forced abstinence and then had a second opportunity to self-administer nicotine, the prenatally-exposed animals showed a significantly greater rate of self-administration than did the controls. Prenatal nicotine exposure causes increased nicotine self-administration, which is revealed only when the animals are allowed to experience a period of nicotine abstinence. This supports a cause-and-effect relationship between the higher rates of smoking in the daughters of women who smoke cigarettes during pregnancy and implicates a role for nicotine in this effect. Our results further characterize the long-term liabilities of maternal smoking but also point to the potential liabilities of nicotine-based treatments for smoking cessation during pregnancy.
孕期母亲吸烟与女性后代日后更高的吸烟风险之间存在显著关联。在动物模型中，产前尼古丁暴露会导致胆碱能和单胺能系统发生持续性改变，这两个系统对于烟草成瘾背后的尼古丁作用都很重要。因此，开展了本研究以确定产前尼古丁暴露与始于青春期的尼古丁自我给药之间是否存在因果关系。在整个妊娠期，通过渗透微型泵输注给怀孕大鼠施用尼古丁（6毫克/千克/天），然后从青春期开始并持续至成年期，让雌性后代通过标准操作性静脉自我给药程序获取尼古丁（0.03毫克/千克/次输注）。妊娠期尼古丁暴露并未改变尼古丁自我给药的初始速率。然而，当动物经历一周的强制戒断，然后有第二次自我给药尼古丁的机会时，产前暴露组动物的自我给药速率显著高于对照组。产前尼古丁暴露会导致尼古丁自我给药增加，这种增加只有在动物经历一段时间的尼古丁戒断后才会显现出来。这支持了孕期吸烟女性女儿中较高吸烟率之间的因果关系，并表明尼古丁在这种效应中起作用。我们的结果进一步描述了母亲吸烟的长期危害，但也指出了孕期基于尼古丁的戒烟治疗的潜在危害。
