Social stress is a risk factor for several stress-related psychopathologies, including post-traumatic stress disorder (PTSD). Sex differences in coping responses contribute to differences between men and women in the prevalence and progression of PTSD symptoms. To advance the field of stress neurobiology, research is needed on the neuronal mechanisms underlying changes in coping behavior and stress resilience. We have shown that establishing social dominance alters neural and behavioral responses to stress differently in male and female Syrian hamsters. Also, neurons in the posteroventral portion of the medial amygdala (MeApv) that send projections to the posterior parts of the bed nucleus of the stria terminalis (BNSTp) modulate responses to threatening stimuli and contribute to sex differences in social behavior. We propose that the development of dominance relationships in both males and females leads to greater activity within a MeA ? BNSTp pathway in dominants compared to subordinates.
In specific aim 1, we hypothesize that elevated activity in a MeApv ? BNSTp pathway during development of social dominance promotes proactive coping responses in females and resistance to social defeat stress in males. In addition, we expect that sex differences arise in the effects of social dominance on stress responsivity because the neural circuits activated during dominance relationships are reactivated in separate situations in males and females.
In specific aim 2, we hypothesize that social defeat stress reactivates a MeApv ? BNSTp pathway in dominant males but not dominant females, which leads to a sex difference in stress resilience (Specific Aim 2). In sum, this project will identify cellular mechanisms and neural circuits that contribute to sex differences in coping responses and stress resilience.

Public Health Relevance

Social stress is a contributing factor in the etiology of neuropsychiatric disorders including major depression, generalized anxiety disorder, and post-traumatic stress disorder. This project focuses on the cellular mechanisms and neural circuits controlling sex differences in coping responses and stress resilience and will aid in the development of interventions that promote healthy responses to stress.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15MH122946-01
Application #
9965559
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Simmons, Janine M
Project Start
2020-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2023-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Tennessee Knoxville
Department
Type
DUNS #
003387891
City
Knoxville
State
TN
Country
United States
Zip Code
37916