Reward and Anxiety: From Rodent Post-Traumatic Stress to Human Psychosocial Stress

摘要

Posttraumatic stress disorder (PTSD) is a chronic disabling condition that results from exposure to traumatic stress. However, although trauma is fairly common, PTSD will only occur in a small proportion of people. This suggests that resilience is a common response to trauma. The neurobiology underlying this adaptive response is thought to involve reward related areas as well as reward functions. This dissertation proposes that reward and reward-related areas have a role in anxiety disorders such as PTSD. This hypothesis was explored using an animal model of PTSD as well as a human mode of psychosical stress. The hypothesis that the ventral tegmental area (VTA), crucial for reward processing, is part of the neural circuitry involved in the symptomatology of PTSD was explored. To assess the role of VTA in PTSD, cells in this area were reversibly inactivated during a single exposure to inescapable foot-shock in a rodent model. Animals that underwent inactivation of VTA neurons decreased avoidance and lowered long-term anxiety-like behaviors in comparison with control groups. To assess short- and long-term electrophysiological effects of trauma on VTA cells, in vivo extracellular recordings were conducted. Results showed that the firing frequency of VTA cells changed both in the short- and long-term, following shock procedures. A human model of psychosical stress was used to test the hypothesis that the ability to respond appropriately to positive stimuli is important for the preservation of positive emotions following stressful events. The results show a positive correlation between trait resilience and trait reward sensitivity. To investigate the link between resilience and reward sensitivity further, the empirical portion of this study used a Monetary Incentive Delay Task (MID) to measure reward sensitivity before and after exposure to a psychosocial stressor. Moreover, behavioral reward sensitivity (as measured by MID and self-report satisfaction after the reward task) also correlated positively with trait and behaviorally measured resilience. The results shown in this dissertation suggest that the neural circuits involved in reward processing and reward function may be involved in resilient responses to stress.