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The effects of angiotensin II receptor antagonism on fear memory and immune cell modulation

Pharmacological inhibition of the renin‐angiotensin system (RAS) is commonly used to treat hypertension and more recently been suggested as a treatment of emotional stress. In a clinical study we have recently shown a role for the RAS in the regulation of the stress response in patients with post‐traumatic stress disorder (PTSD). Psychological stress is also known to perturb the homeostasis of the immune system. The purpose of this study was to further examine the role of RAS in an animal model of PTSD and its impact on the immune system. We performed Pavlovian fear conditioning pairing auditory cues with footshocks to examine the effects of the angiotensin II receptor antagonist Losartan (1mg/kg and 10mg/kg) on fear memory extinction. 24 h after fear conditioning, Losartan was administered 1h prior to fear memory extinction training. While no effect of Losartan was observed on extinction training, there was a significant decrease in fear as measured by freezing behavior to the auditory cue when tested the following day (14.9% vs 27.3%; p<0.05). Immune cells of the spleen were quantified using flow cytometry and Losartan treated mice exhibited significantly fewer CD45+CD11b+ (macrophage– like) cells (p<0.05). These data suggest that the RAS may contribute to the retention of extinction fear memory and alter the effectiveness of the immune system to respond to a challenge.