Using drugs of abuse while pregnant has tremendous negative consequences for the offspring, including an enhanced risk for substance use disorder (SUD). This vulnerability suggests that gestational exposure to drugs alters the developmental trajectory of neurons important in SUD processes, which could lead to later life changes in responsiveness to motivationally salient stimuli. The laterodorsal tegmentum (LDT) gates the behaviorally relevant firing pattern signaling stimuli saliency in mesoaccumbal circuits. Accordingly, any alterations in LDT functionality could alter output, and play a role in negative outcomes on motivated behavior associated with early-life nicotine exposure. Therefore, we investigated whether prenatal exposure to nicotine (PNE), which is a known teratogen, altered responsiveness of LDT neurons to alcohol by conducting electrophysiology in brain slices. Alcohol induced an outward current in control LDT cells, which was not seen in PNE LDT neurons. The frequency of mEPSCs was significantly decreased by alcohol in LDT PNE cells and accompanied by a decrease in action potential frequency, which were actions not seen in controls. Changes in baseline activity of PNE LDT cells were also observed. In summary, PNE LDT neurons showed alterations in baseline activity and membrane and synaptic responses to postnatal exposures to alcohol. The differences in PNE baseline activity and alcohol responses likely lead to differential output from the LDT to mesoaccumbal targets that could play a role in biasing coding of relevant stimuli, which could participate in the enhanced proclivity for development of SUD in those exposed during gestation to nicotine.

在怀孕期间使用滥用药物会对后代产生巨大的负面影响，包括增加物质使用障碍 (SUD) 的风险。这种脆弱性表明，妊娠期药物暴露会改变在 SUD 过程中重要的神经元的发育轨迹，这可能导致晚年对显着动机的反应发生变化。背侧被盖 (LDT) 门控着在 mesoaccumbal 电路中与行为相关的放电模式信号刺激显着性。因此，LDT 功能的任何改变都可能改变输出，并在与生命早期尼古丁暴露相关的动机行为的负面结果中发挥作用。因此，我们调查了产前暴露于尼古丁（PNE），这是一种已知的致畸剂，通过在脑切片中进行电生理学改变 LDT 神经元对酒精的反应。酒精在对照 LDT 细胞中诱导外向电流，这在 PNE LDT 神经元中未见。在 LDT PNE 细胞中，酒精显着降低了 mEPSCs 的频率，并伴随着动作电位频率的降低，这是在对照组中未见的作用。还观察到 PNE LDT 细胞基线活性的变化。总之，PNE LDT 神经元表现出对出生后暴露于酒精的基线活动和膜和突触反应的改变。PNE 基线活动和酒精反应的差异可能导致从 LDT 到 mesoaccumbal 目标的不同输出，这可能在相关刺激的编码偏差中发挥作用，