ESR1 and Anxiety: Pharmacological stimulation with PPT increases anxiety-like behavior.60,61 Downregulation of ERα induced by delivery of an adeno-associated viral vector into the medial preoptic area and posterodorsal amygdala of GDX rats showed decreased anxiety-like behavior in open field and light/dark box tests.62 Global knockout of ERα does not appear to influence anxiety-like behavior in female mice,63 but increases it in males,64 indicating possible sex differences in the actions of ERα.