NR3C1 and Anxiety: However, a previous study showed that istradefylline inhibited anxiety and stress caused by maternal separation through neuromodulation of the hypothalamic–pituitary–adrenal axis (HPA-axis), where A2AR antagonism resulted in a reduction in plasma corticosteroid levels and decreased surface expression of hippocampal glucocorticoid receptors, which were elevated following stress conditions [56].