Exposure to stressful events is a key factor in the etiology of several affective disorders, including post-traumatic stress disorder. Importantly, not all individuals exposed to stressful events develop stress- related mental illness, and there is considerable interest in what makes some individuals vulnerable and others resilient. In this proposal, we will investigate the mechanisms controlling resistance to social stress using a social defeat model in Syrian hamsters, called conditioned defeat. In our animal model, social defeat results in a complete loss of species-typical territorial aggression and a substantial increase in submissive and defensive behavior when individuals are later tested with a non-aggressive intruder. Recently, we tested individuals with established dominance relationships in our conditioned defeat model and found that dominant animals showed less submissive and defensive behavior at testing compared to subordinates and controls. These results suggest that the dominant social status is associated with resistance to the development of defeat-induced changes in behavior. Also, we have recently found that dominant animals show increased c-Fos expression in the infralimbic cortex (ILC) after social defeat compared to subordinates. These results suggest that resistance to conditioned defeat in dominant animals is associated with neural activation in the ILC during social defeat training. Interestingly, neura activity in the ILC has been linked to stress resilience and is thought to regulate affective processing by inhibiting the basolateral amygdala (BLA). In this proposal we will test the overarching hypothesis that neural activity in the ILC during social defeat disrupts neural plasticity within the BLA and thereby impairs the development of conditioned defeat in dominant hamsters. Specifically, we will test three predictions. First, we will test the prediction that pharmacological inactivation of the ILC prior to social defeat will increase CD and increase defeat-induced BDNF mRNA expression in the BLA in dominant animals only. Second, we will inject the retrograde tracer Cholera Toxin B (CTB) into the BLA and test the prediction that dominant hamsters will show an increased proportion of ILC cells double-labeled for c-Fos and CTB following social defeat compared to subordinates and controls. Third, we will investigate the time course of CD resistance by testing the prediction that dominant hamsters will show reduced CD and increased neural activation in the ILC following social defeat compared to subordinates only after they experience 14 days, and not 1 or 7 days, of dominance encounters.

Public Health Relevance

Exposure to stressful events can lead to a variety of psychiatric disorders, including post-traumatic stress disorder. In this proposal we will investigate the mechanisms by which dominant social status protects individuals against future social stress. Research such as this will improve our understanding of the neural mechanisms that mediate resiliency, and ultimately should lead to improved treatment options for stress-related mental illness.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
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Simmons, Janine M
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University of Tennessee Knoxville
Schools of Arts and Sciences
United States
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Clinard, Catherine T; Barnes, Abigail K; Adler, Samuel G et al. (2016) Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters. Horm Behav 86:27-35
Burleson, Cody A; Pedersen, Robert W; Seddighi, Sahba et al. (2016) Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood. Behav Neurosci 130:437-47
Cooper, M A; Clinard, C T; Morrison, K E (2015) Neurobiological mechanisms supporting experience-dependent resistance to social stress. Neuroscience 291:1-14
Clinard, Catherine T; Bader, Lauren R; Sullivan, Molly A et al. (2015) Activation of 5-HT2a receptors in the basolateral amygdala promotes defeat-induced anxiety and the acquisition of conditioned defeat in Syrian hamsters. Neuropharmacology 90:102-12
Morrison, Kathleen E; Bader, Lauren R; Clinard, Catherine T et al. (2014) Maintenance of dominance status is necessary for resistance to social defeat stress in Syrian hamsters. Behav Brain Res 270:277-86
Morrison, Kathleen E; Bader, Lauren R; McLaughlin, Colleen N et al. (2013) Defeat-induced activation of the ventral medial prefrontal cortex is necessary for resistance to conditioned defeat. Behav Brain Res 243:158-64