主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Post-traumatic stress disorder (PTSD) is a debilitating neuropsychological disorder that develops as a result of exposure to physical or psychological trauma. Emerging evidence suggests that PTSD is a strong predictor of cardiovascular disease (CVD). Recent clinical studies suggest that blockade of the renin-angiotensin system (RAS) crucial to blood pressure control and fluid homeostasis reduces the severity of PTSD symptoms. We have also demonstrated in a preclinical mouse model of PTSD (Pavlovian fear conditioning) that angiotensin type 1 receptor (AT1R) inhibition attenuates conditioned fear responses and facilitates the extinction of conditioned fear. Both AT1Rs and angiotensin type 2 receptors (AT2Rs) are expressed in the amygdala, a brain region critical for fear learning and extinction. Whether different brains AT receptor subtypes play a role in stress disorders such as PTSD is largely unknown, as is their impact on cardiovascular dysfunction in fear. Our preliminary studies indicate, however, that activation and inhibition of brain AT2Rs have opposing effects on the expression of fear memory in a preclinical mouse model of PTSD. This talk will discuss the role of endogenous brain angiotensin II, its receptors (AT1R and AT2R) and downstream signaling pathways in fear memory and associated cardiovascular measures of conditioned fear. Our working hypothesis is that the expression and activity of brain angiotensin II and its receptors (AT1R / AT2R) are differentially and dynamically regulated during the consolidation and recall of fear memory, and that these changes contribute to the balance of excitatory (fear-on) and inhibitory (fear-off) signals required for the storage and retrieval of conditioned fear memories. The overall goal of these studies is to further elucidate the mechanism(s) by which the angiotensin system acts as an important and novel mediator of PTSD pathology, and will provide new targets and opportunities for pharmacological interventions in PTSD and PTSD-related CVD co-morbidity.
