Among the most prevalent of mental afflictions, anxiety disorders are more commonly diagnosed in women than in men. There is ample evidence that circulating levels of gonadal steroid hormones, including estrogens such as estradiol and androgens such as testosterone, can reduce anxiety in humans and so may play a role in the sex difference in anxiety disorders. Laboratory mice also show a sex difference in anxiety- like behaviors that, as with anxiety in humans, are reduced by circulating testosterone. In mice, it is clear that circulating levels of steroids modulate anxiety-like behaviors. We want t perform exploratory experiments to determine which brain regions are being affected by hormones to reduce anxiety-like behaviors in mice. Preliminary observations suggest that two plausible brain sites for modulating anxiety, the medial prefrontal cortex and the hippocampus, are not the sites responding to testosterone. Other observations implicate the basolateral amygdala as a potential site of hormone action and we would like to conduct experiments to confirm or refute these indications. Understanding how gonadal hormones act on the brain to reduce anxiety in mice may suggest new therapeutic approaches for anxiety disorder in humans.
We have found that androgenic hormones like testosterone act through androgen receptors to reduce anxiety in laboratory rats and mice. We will use new technologies to selectively disable the androgen receptor gene to ask which brain regions respond to testosterone to allay anxiety. This research could help us understand why women are more likely than men to suffer from anxiety disorders.
