Paz Rodrigo, Barsness Brigg, Martenson Trevor, Tanner Daniel, Allan Andrea M
Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131-0001, USA.
Neuropsychopharmacology. 2007 Mar;32(3):693-9. doi: 10.1038/sj.npp.1301066. Epub 2006 Mar 22.
Prenatal nicotine exposure (PNE) has been associated with increased prevalence of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) and substance abuse in exposed children and adolescents. Whether these syndromes are caused by nicotine exposure, or genetic and psychosocial adversities associated with maternal smoking is not completely clear. Animal models suggest a direct impact of PNE. However, the fact that nicotine is forcefully administrated in these paradigms raises some questions about the specificity of these findings. Pregnant C57BI/6J mice were allowed to choose drinking saccharin/nicotine solutions or pure water. Controls could choose saccharin solutions or pure water. Offspring were tested in spontaneous locomotion, fear-associated learning (trace conditioning), addictive (conditioned place preference), and depression-like (learned helplessness) behaviors. There was no significant difference in weight or pup number between the prenatal treatment groups. A significant effect of PNE was observed on spontaneous locomotion, preference for a cocaine-associated place, and latency to escape in the learned helplessness paradigm. Surprisingly, PNE mice exhibited an increased learning of trace-conditioned fear-associated cues. The hyperlocomotive behavior reported in animal models of PNE is not likely an artifact of forceful nicotine administration. The increased prevalence of ADHD, MDD and substance abuse observed in PNE children and adolescents is probably caused by direct behavioral teratogenic effects of PNE. The role of PNE as a risk factor of syndromes associated to increased learning of fear-associated cues such as post-traumatic stress disorder (PTSD) warrants further evaluation.
产前尼古丁暴露（PNE）与暴露儿童和青少年中注意力缺陷多动障碍（ADHD）、重度抑郁症（MDD）和药物滥用的患病率增加有关。这些综合征是由尼古丁暴露引起的，还是与母亲吸烟相关的遗传和心理社会逆境所致，目前尚不完全清楚。动物模型表明PNE有直接影响。然而，在这些实验范式中强行给予尼古丁这一事实对这些研究结果的特异性提出了一些疑问。让怀孕的C57BI/6J小鼠选择饮用糖精/尼古丁溶液或纯水。对照组可以选择糖精溶液或纯水。对后代进行自发运动、恐惧相关学习（痕迹条件反射）、成瘾（条件性位置偏爱）和抑郁样（习得性无助）行为测试。产前治疗组之间在体重或幼崽数量上没有显著差异。观察到PNE对自发运动、对与可卡因相关位置的偏爱以及在习得性无助范式中的逃避潜伏期有显著影响。令人惊讶的是，PNE小鼠对痕迹条件性恐惧相关线索的学习增加。PNE动物模型中报道的运动亢进行为不太可能是强行给予尼古丁的人为结果。在PNE儿童和青少年中观察到的ADHD、MDD和药物滥用患病率增加可能是由PNE的直接行为致畸作用引起的。PNE作为与恐惧相关线索学习增加相关综合征（如创伤后应激障碍（PTSD））的危险因素的作用值得进一步评估。
