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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH104780-01A1
Application #
8893535
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Simmons, Janine M
Project Start
2015-04-01
Project End
2017-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
1
Fiscal Year
2015
Total Cost
$223,887
Indirect Cost
$73,887
Name
Michigan State University
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
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Chen, Chieh V; Brummet, Jennifer L; Lonstein, Joseph S et al. (2014) New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice. Horm Behav 65:211-8