Smoking during pregnancy is associated with deleterious physiological and cognitive effects on the offspring, which are likely due to nicotine‐induced alteration in the development of neurotransmitter systems. Prenatal nicotine exposure (PNE) in rodents is associated with changes in behaviors controlled in part by the pontine laterodorsal tegmentum (LDT), and LDT excitatory signaling is altered in a sex and age‐dependent manner by PNE. As effects on GABAergic LDT signaling are unknown, we used calcium imaging to evaluate GABA_A receptor‐ (GABA_AR as well as GABA_A‐_ρR) and GABA_B receptor (GABA_BR)‐mediated calcium responses in LDT brain slices from female and male PNE mice in two different age groups. Overall, in older PNE females, changes in calcium induced by stimulation of GABA_AR and GABA_BR, including GABA_A‐_ρR were shifted toward calcium rises. In both young and old males, PNE was associated with alterations in calcium mediated by all three receptors; however, the GABA_AR was the most affected. These results show for the first time that PNE is associated with alterations in GABAergic transmission in the LDT in a sex‐ and age‐dependent manner, and these data are the first to show PNE‐associated alterations in functionality of GABA receptors in any nucleus. PNE‐associated alterations in LDT GABAergic transmission within the LDT would be expected to alter output to target regions and could play a role in LDT‐implicated, negative behavioral outcomes following gestational exposure to smoking. Accordingly, our data provide further supportive evidence of the importance of eliminating the consumption of nicotine during pregnancy.

中文翻译：

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异味后背盖膜中GABA受体介导的反应的性别特异性改变与产前暴露于尼古丁有关。

怀孕期间吸烟与对后代的有害生理和认知影响有关，这很可能是由于尼古丁引起的神经递质系统发育改变所致。啮齿类动物的产前尼古丁暴露（PNE）与行为的变化部分地由桥脑后背盖膜（LDT）控制，并且PDT改变了LDT兴奋性信号的性别和年龄依赖性。作为GABA能LDT信令影响是未知的，我们使用钙成像来评估GABA_甲受体（GABA_甲R作为以及GABA_甲- _ρ R）和GABA_乙GABA受体（_乙R）介导的两个不同年龄组的雌性和雄性PNE小鼠的LDT脑片中的钙反应。总体而言，在老年PNE女性中，由GABA _A R和GABA _B R的刺激（包括GABA _A - _{ρR）引起的}钙变化朝钙的增加方向移动。在年轻和老年男性中，PNE均与所有三种受体介导的钙改变有关。但是，GABA _AR受的影响最大。这些结果首次表明PNE与LDT中的LABA的GABA能传递具有性别和年龄依赖性，并且这些数据是第一个显示PNE相关的任何核中GABA受体功能改变的数据。LDT中PNE相关的变化LDT内的GABA能传递可望改变向目标区域的输出，并可能在妊娠暴露于吸烟后与LDT相关的负面行为结果中起作用。因此，我们的数据提供了进一步的支持性证据，证明了在怀孕期间消除尼古丁的消耗非常重要。