Victory, Defeat and the Role of Testosterone in Social Behaviors and Internal States in Mice

Abstract

The hormone testosterone (T) is believed to be involved in facilitating a variety of social behaviors and internal states in humans, including aggression, dominance, anxiety and depression. Mouse models have been developed to mimic these behaviors and states, which appear to have similar relationships with T in mice. The outcomes of aggressive encounters, namely victory or defeat, have wide-ranging effects on testosterone levels, aggression, and pathologies, such as anxiety and depression. This project seeks to provide further clarity on this topic by carrying out a slate of new experimental research relevant to the gaps in previous knowledge. Despite expectations that dominance status would be predictive of behaviors related to aggression and anxiety, no such connections were found. Nevertheless, T was found to play a role in all of these states. In the novelty suppressed feeding test, used to measure anxiety and depressive symptoms in mice, there was a correlation between naturally produced testosterone and fast retrieval of the food reward. Although no correlation was found between dominance status and natural T levels, T pulse injections before encounters appeared to improve dominance rank in subordinate animals. These T pulses also increased aggressive behavior in subordinate animals relative to control subordinates. Furthermore, T appears to play a role in behaviors observed during the chronic social defeat stress (CSDS) protocol used for producing a depressive state in mice. Natural T levels correlated with defensive aggression that predicted resilience to the depressive phenotype. Further research should consider whether the administration of T pulses before the daily defeats in CSDS could boost aggressive behavior and dominance during these encounters and protect against the depressive-like behavior changes observed following CSDS.