Prior research and human literature indicate that coping or the perception of control often mitigates the consequences of stressful experiences, but lack or control during stress may result in pathological responses. In the rat, much is known about the basic neural mechanisms that mediate the effects of controllable and uncontrollable stressors. Importantly, uncontrollable stressors cause activation of the serotonergic dorsal raphe nucleus while controllable stressors prevent this activation via inhibitory modulation from the ventromedial prefrontal cortex (PFC;Maier et al., 2006). Building upon this knowledge, the proposed research will determine how these mechanisms interact with the amygdala, a structure critical to anxiety states.
The specific aims of this proposal will inform the basic understanding of how stress and coping affect anxiety on behavioral and neural levels and contribute to 3 of the 6 high-priority research areas of the NIMH Division of Neuroscience and Basic Behavioral Science.
The aims have significant relevance to the Affect and Social Behavior program because the behavioral and neural components of stressor controllability and anxiety are similar to the condition in human PTSD patients. In these patients PFC activity is reduced and amygdala activity is increased, providing a mechanism for hyperanxiogenic responses to even mildly-emotional stimuli (Bremner et al., 1997). The results of this research could facilitate advancements in treatment, diagnosis and prevention of PTSD in humans. Research Design: In brief, rats will be exposed to a stressor and then tested for anxiety using a social exploration test. Social exploration is reduced under anxiogenic conditions. A variety of methods will be used to determine the contributions of selected brain nuclei, including: microinjection of excitatory or inhibitory compounds during stress, in vivo microdialysis, functional anatomy using retrograde tracing and immunohistochemistry for cellular activity markers. Together, these methods provide multiple levels of analysis of anxiety and the components of the neural systems that mediate the consequences of controllable or uncontrollable stressors. Relevance: According to NIMH publication OM-99 4157 (Revised), 3.6 % of American adults suffer from PTSD. Traumatic events include military conflict, hurricanes, acts of terrorism, illness, injury, physical abuse and criminal violence. However, these experiences do not leave all victims crippled with PTSD. The proposed research will provide critical insight to how the key psychological variable of coping contributes to the development or prevention of anxiety/PTSD after a traumatic event.
