Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Transl Psychiatry. 2022 Aug 19;12(1):338. doi: 10.1038/s41398-022-02043-4.
Daily, individuals select actions based on cost-benefit to allocate resources into goal-directed actions. Different brain regions coordinate this complex decision, including the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and ventral tegmental area (VTA). In utero exposure to synthetic glucocorticoids (iuGC), such as dexamethasone, triggers prominent motivation deficits but the impact of this exposure in the ACC-NAc and/or ACC-VTA circuits is unknown. Here, we show that iuGC exposure causes decreased motivation for natural rewards (food) and impaired effort-based decision-making. Importantly, reduced neuronal activation (number of c-fos neurons) was observed in the NAc core and ACC of iuGC rats in comparison to CTR rats after performing the effort-based decision-making task. In addition, iuGC treatment led to increased NAc and ACC basal neuronal activity. Electrophysiological recordings during optogenetic modulation of ACC terminals in the NAc revealed that the ACC-NAc circuit is dysfunctional in iuGC animals. These data suggest that iuGC animals present motivational and effort-based decision-making deficits that can be associated with the observed ACC-NAc dysfunction.
个体每天都会根据成本效益来选择行动，将资源分配到目标导向的行动中。不同的大脑区域协调这一复杂的决策，包括伏隔核（NAc）、前扣带皮层（ACC）和腹侧被盖区（VTA）。在子宫内暴露于合成糖皮质激素（如地塞米松）会引发明显的动机缺陷，但这种暴露对 ACC-NAc 和/或 ACC-VTA 回路的影响尚不清楚。在这里，我们表明 iuGC 暴露会导致对自然奖励（食物）的动机降低和基于努力的决策受损。重要的是，与 CTR 大鼠相比，在执行基于努力的决策任务后，iuGC 大鼠的 NAc 核心和 ACC 中的神经元激活（c-fos 神经元数量）减少。此外，iuGC 处理导致 NAc 和 ACC 的基础神经元活动增加。在 NAc 中的 ACC 末端进行光遗传学调节期间的电生理记录显示，iuGC 动物的 ACC-NAc 回路功能失调。这些数据表明，iuGC 动物表现出动机和基于努力的决策缺陷，这可能与观察到的 ACC-NAc 功能障碍有关。
