NEUROBEHAVIORAL PHENOTYPING OF MALE AND FEMALE RATS TO BOP, HIFU, AND STRESS

The wars in Iraq and Afghanistan are taking physical and psychological tolls on American service members. Fifteen to thirty percent of returning Warriors have been diagnosed with TBI and 40% returning Troops have been diagnosed with mental health problems (including anxiety, depression, and substance abuse). Moderate to severe stress is comorbid with TBI. The purpose of this research project is to evaluate effects of mTBI and stress on behavioral and neurochemical responses at two time points after injury in male and female rats. The specific aims of this project are to: (1) characterize the behavioral phenotype of mTBI in rats; (2) compare responses of male and female rats; (3) compare responses with and without exposure to stress; and (4) compare behavioral phenotypes with biological responses. This research project is investigating effects of injury; stress; sex; and time after injury (1-4 or 8-11 days). Injury is manipulated by blast overpressure (BOP) to model effects of blast waves from improvised explosive devices (IED) without shrapnel or penetrating injury. Stress is manipulated using the Warrior Stress Paradigm (WSP) that combines predator stress (exposure to synthetic fox urine) and unpredictable environmental stimuli (e.g., noise, lights). WSP is designed to model the Warriors¿ stress exposure to unpredictable threats of death and disruptive environmental stimuli. Subjects are assessed behaviorally pre- and post-injury and blood and brain samples are collected post-mortem for analyses. The behavioral dependent variables measure movement, sensory and motor reflexes, balance, attention, memory, nociception, and anxiety- and depression-related behaviors. Blood is assayed for corticosterone, adrenocorticotropic hormone (ACTH), prolactin, cytokines and chemokines. Brain samples are micropunched from: orbital frontal cortex, prefrontal cortex, insula cortex, hippocampus, amygdala, nucleus accumbens, and ventral segmental area and assayed for total protein, catecholamines and their metabolites (DA, DOPAC, HVA, NE) and serotonin and its metabolites (5HT, 5HIAA). Electrophysiological recording from the hippocampus and amygdala provide additional information about neurobiological activity in these brain regions relevant to memory and emotion.