University of California, Los Angeles, Department of Psychiatry, United States; University of California, Irvine, Graduate Division, United States.
University of California, Irvine, School of Biological Sciences, United States.
Neuropharmacology. 2018 Jun;135:529-535. doi: 10.1016/j.neuropharm.2018.04.010. Epub 2018 Apr 9.
The objective of the current study is to test the hypothesis that the deletion of alpha(α)2* nicotinic acetylcholine receptors (nAChRs) (encoded by the Chrna2 gene) ablate maternal nicotine-induced learning and memory deficits in adolescent mice. We use a pre-exposure-dependent contextual fear conditioning behavioral paradigm that is highly hippocampus-dependent. Adolescent wild type and α2-null mutant offspring are exposed to vehicle or maternal nicotine exposure (200 μg/ml, expressed as base) in the drinking water throughout pregnancy until weaning. Adolescent male offspring mice are tested for alterations in growth and development characteristics as well as modifications in locomotion, anxiety, shock-reactivity and learning and memory. As expected, maternal nicotine exposure has no effects on pup number, weight gain and only modestly reduces fluid intake by 19%. Behaviorally, maternal nicotine exposure impedes extinction learning in adolescent wild type mice, a consequence that is abolished in α2-null mutant mice. The effects on learning and memory are not confounded by alternations in stereotypy, locomotion, anxiety or sensory shock reactivity. Overall, the findings highlight that the deletion of α2* nAChRs eliminate the effects of maternal nicotine exposure on learning and memory in adolescent mice.
本研究的目的是验证这样一个假设，即α2烟碱型乙酰胆碱受体（由 Chrna2 基因编码）的缺失可消除母源性尼古丁暴露对青春期小鼠学习和记忆的损害。我们使用了一种预先暴露依赖性的情境性恐惧条件反射行为范式，该范式高度依赖于海马体。青春期野生型和 α2 敲除突变体后代在整个怀孕期间直至断奶期间，通过饮用水暴露于载体或母源性尼古丁（200μg/ml，以碱计）。青春期雄性后代小鼠的生长和发育特征以及运动、焦虑、应激反应和学习记忆的变化都会被检测到。正如预期的那样，母源性尼古丁暴露对幼仔数量、体重增加没有影响，仅使液体摄入量适度减少 19%。行为上，母源性尼古丁暴露会阻碍青春期野生型小鼠的消退学习，而这种影响在 α2 敲除突变体小鼠中被消除。学习和记忆的这些变化不受刻板行为、运动、焦虑或感觉应激反应的改变所混淆。总的来说，这些发现强调了 α2烟碱型乙酰胆碱受体的缺失可消除母源性尼古丁暴露对青春期小鼠学习和记忆的影响。
