Abstract

Independent of their beneficial effects on hypertension and cardiovascular related disease, angiotensin receptor type 1 (AT1R) blockers can improve stress-related symptoms. 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 losartan treated animals. 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. 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. 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. 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.

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