Neuroendocrine and Gene Expression Changes are Associated with Different Phenotypic Responses to Juvenile Social Defeat

Rebecca K. Huda, Maeson S. Latsko, Laure A. Farnbauch, Aaron M. Jasnow

Following trauma, 15-20% of subjects develop stress-related pathologies (e.g., post-traumatic stress disorder (PTSD), depression). Stress, particularly social stress, during periadolescence can exacerbate symptoms of adult psychopathologies. In the current study, we use an acute defeat paradigm to investigate effects of social stress on subsequent social behavior. Defeats involve exposing juvenile experimental male C57Bl6/J mice to aggressive CD-1 mice. For each round, experimental mice receive 5 minutes of physical contact followed by 55 minutes of sensory contact across a Plexiglas divider. Control mice receive only sensory contact. Mice are exposed to eight rounds over two consecutive days. One day and thirty days after social defeat, mice are tested for social interaction. In prior studies, adult social defeat results in two phenotypic responses in experimental mice; some mice display high interaction levels (resistance) and others display low interaction levels (susceptibility). Following juvenile social defeat, mice are initially resistant. However, when tested as adults, two phenotypic responses emerge; latent susceptibility or stable resistance. To investigate the development of these phenotypes overtime, we examined neuroendocrine responses to defeat and social interaction across the life-span. Stable resistant mice display elevated corticosterone following juvenile social interaction compared to control and susceptible mice. Stable resistant mice also display reduced testosterone as adults compared to latent susceptible mice. Future experiments will analyze gene expression changes in glucocorticoid receptors and corticotropin releasing hormone receptors using in situ hybridization. By measuring markers associated with elevated stress, we will help determine how early life stress influences ontogeny of maladaptive behavioral outcomes.