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Post-traumatic stress disorder (PTSD) is prevalent in women; however, preclinical research on PTSD has predominantly been conducted in male animals. Using a predator scent stress (PSS) rodent model of PTSD, we sought to determine if stress-susceptible female rats show altered monoamine concentrations in brain regions associated with PTSD: the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and dorsal (dHIPP) and ventral (vHIPP) hippocampus. Female Sprague–Dawley rats were exposed to a single, 10-min PSS exposure and tested for persistent anhedonia, fear, and anxiety-like behavior over four weeks. Rats were phenotyped as stress-susceptible based on sucrose consumption in the sucrose preference task and time spent in the open arms of the elevated plus maze. Brain tissue was collected, and norepinephrine, dopamine, serotonin, and their metabolites were quantified using high-performance liquid chromatography. Stress-susceptibility in female rats was associated with increased dopamine and serotonin turnover in the mPFC. Susceptibility was also associated with elevated dopamine turnover in the NAc and increased norepinephrine in the vHIPP. Our findings suggest that stress-susceptibility after a single stress exposure is associated with long-term effects on monoamine function in female rats. These data suggest interventions that decrease monoamine turnover, such as MAOIs, may be effective in the treatment of PTSD in women.

OBJECTIVES/GOALS: Post-traumatic stress disorder (PTSD) develops in a subset of individuals (15-25%) exposed to trauma. We report our preliminary findings investigating underlying peripheral immune responses related to risk and resilience to PTSD. METHODS/STUDY POPULATION: Sprague-Dawley rats (half male) were exposed to predator scent stress in the form of the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) once for 10 minutes. Seven days later, rats were assessed for persistent anxiety-like behavior using the acoustic startle response task (ASR) and elevated plus maze (EPM). Tail blood was collected for later inflammation analysis at three time points: 1) prior to experiment start, 2) after TMT exposure, and 3) after ASR and EPM. Using a with-in subjects design, our experiment elucidates the connection between PTSD-like symptoms and baseline immune function, inflammatory stress responses, and chronic inflammatory state after stress exposure. RESULTS/ANTICIPATED RESULTS: In comparison to healthy controls, humans with PTSD show elevated blood levels of inflammatory markers. Human studies also show a relationship between baseline immune dysfunction and later PTSD development. In agreement with this literature, we anticipate PTSD-like rats will have increased blood levels of inflammation markers at all three time points compared to resilient and control rats. These findings will back-translate human findings in support of the predator scent stress preclinical model of PTSD. DISCUSSION/SIGNIFICANCE: Our findings will elucidate the temporal aspects of proinflammatory markers and PTSD development. This study will indicate if baseline peripheral immune dysfunction, inflammatory response immediately after stress exposure, and/or chronic inflammatory state predicts ptsd-like behavior in rats.