Divergent angiotensin receptor signaling in a mouse model of post-traumatic stress disorder (PTSD)

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC252

Poster Communications: Divergent angiotensin receptor signaling in a mouse model of post-traumatic stress disorder (PTSD)

P. J. Marvar1

1. Pharmacology and Physiology, George Washington University, Washington, District of Columbia, United States.

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Background: Independent of their beneficial effects on hypertension and cardiovascular related disease, angiotensin receptor type 1 (AT1R) blockers can improve stress-related symptoms (Saavedra JM et al., 2012). AT1R receptor-mediated actions can be counteracted directly or indirectly by the angiotensin receptor type 2 receptor (AT2R). Our recent studies in a mouse model of PTSD have shown that AT1R blockade increases the extinction (learned inhibition) of a traumatic fear memory and that AT1R mRNA expression is reduced in fear related brain regions of animals treated with the AT1R antagonist losartan (Marvar et al., 2014). These data imply that downstream AT1 signaling events maybe important in consolidation of fear memory extinction. Therefore we investigated the acute effects of AT2R inhibition on fear memory and baseline anxiety in mice. Methods: We performed classical Pavlovian fear conditioning pairing auditory cues with foot shocks and examined fear extinction behavior and cardiovascular responses in the presence of the AT2R antagonist PD 123319. Results: Twenty-four hours following fear conditioning, PD 123319 (15 mg/kg IP) was administered prior to fear memory extinction. The PD treated group exhibited significantly less freezing behavior (F10, 300 = 1.9; p<0.05) during fear expression and contrary to our previous results with the AT1 antagonist losartan, there was no effect during extinction retention, an index of long-term fear memory. Moreover, qPCR data revealed that mRNA expression in the central amygdala of AT2R and angiotensin converting enzyme 2 (ACE2) are elevated following fear conditioning, whereas the AT1R gene expression pathways are unaltered. Conclusion: These data indicate that AT1R and AT2R may have divergent effects on short and long-term fear memory formation. Further studies are required to understand the differential regulation of angiotensin receptor signaling in PTSD.



Where applicable, experiments conform with Society ethical requirements.

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