The role of the androgen receptor in anxiety-related behaviors, the hypothalamic pituitary adrenal axis, and sensorimotor gating: Studies in rodents with the testicular feminization mutation

Androgens such as testosterone play a role in the display of anxiety-related behaviors and sensorimotor gating. However, the role of a specific hormone receptor, the androgen receptor (AR) in the regulation of these behaviors is less clear, because testosterone can be converted to estrogens that act on estrogen receptors. In this series of experiments we investigated the role of the AR in anxiety and sensorimotor gating by comparing AR deficient male mice and rats with the testicular feminization mutation (Tfm) to their wild type siblings in rodent models of these behaviors. Since increased anxiety-related behaviors are often correlated with an elevation of the hypothalamic-pituitary-adrenal (HPA) axis we also measured the release of the adrenal stress hormone corticosterone at baseline and at time points after exposure to an anxiety-provoking situation. Results of these studies indicate increased indices of anxiety and increased activation of the HPA axis in both Tfm male rats and mice, while sensorimotor gating appeared normal in the absence of ARs. An investigation into the role of androgens and the AR prior to adulthood in the organization of anxiety-related behaviors and sensorimotor gating revealed that neonatally gonadectomized Tfm and wt male rats showed decreased anxiety-related behavior and increased sensorimotor gating compared to neonatally sham operated Tfm and wt males. These results suggest that androgens act primarily via an AR-independent mechanism, perhaps through estrogen receptors, during development to influence these behaviors. Together our findings in Tfm rodents indicate a role of the AR and/or developmental androgens in the regulation of anxiety-related behavior, the HPA axis, and sensorimotor gating.