Learning of probabilistic punishment as a model of anxiety produces changes in action but not punisher encoding in the dmPFC and VTA.

Previously, we developed a novel model for anxiety during motivated behavior by training rats to perform a task where actions executed to obtain a reward were probabilistically punished and observed that after learning, neuronal activity in the ventral tegmental area (VTA) and dorsomedial prefrontal cortex (dmPFC) represent the relationship between action and punishment risk (Park and Moghaddam, 2017). Here, we used male and female rats to expand on the previous work by focusing on neural changes in the dmPFC and VTA that were associated with the learning of probabilistic punishment, and anxiolytic treatment with diazepam after learning. We find that adaptive neural responses of dmPFC and VTA during the learning of anxiogenic contingencies are independent from the punisher experience and occur primarily during the peri-action and reward period. Our results also identify peri-action ramping of VTA neural calcium activity, and VTA-dmPFC correlated activity, as potential markers for the anxiolytic properties of diazepam.

Co-occurrence of preconception maternal childhood adversity and opioid use during pregnancy: Implications for offspring brain development.

Understanding of the effects of in utero opioid exposure on neurodevelopment is a priority given the recent dramatic increase in opioid use among pregnant individuals. However, opioid abuse does not occur in isolation-pregnant individuals abusing opioids often have a significant history of adverse experiences in childhood, among other co-occurring factors. Understanding the specific pathways in which these frequently co-occurring factors may interact and cumulatively influence offspring brain development in utero represents a priority for future research in this area. We highlight maternal history of childhood adversity (CA) as one such co-occurring factor that is more prevalent among individuals using opioids during pregnancy and which is increasingly shown to affect offspring neurodevelopment through mechanisms beginning in utero. Despite the high incidence of CA history in pregnant individuals using opioids, we understand very little about the effects of comorbid prenatal opioid exposure and maternal CA history on fetal brain development. Here, we first provide an overview of current knowledge regarding effects of opioid exposure and maternal CA on offspring neurodevelopment that may occur during gestation. We then outline potential mechanistic pathways through which these factors might have interactive and cumulative influences on offspring neurodevelopment as a foundation for future research in this area.