IGF1R and Anxiety: For example, as EE impacted memory and GAD expression herein, E2 has also been shown to increase GAD mRNA levels in the hippocampus, regulate GABAergic activity, initiate IGF1-R signaling (Weiland, 1992; Murphy et al., 1998; Nakamura et al., 2004; Garcia-Segura et al., 2007), increase hippocampal IGF1-R expression (Witty et al., 2013), improve working memory, and decrease anxiety-like behavior following Ovx (Bimonte and Denenberg, 1999; Hiroi et al., 2006, 2016; Hiroi and Neumaier, 2006).