Contributions of the Renin Angiotensin System to Fear Memory and Fear Conditioned Cardiovascular Responses
Open AccessAnxiety disorders, such as Posttraumatic stress disorder (PTSD), are associated with an increased risk of developing cardiovascular disease. While the exact mechanisms underlying this relationship are not entirely clear, recent evidence suggests that a hormonal system involved in the maintenance of blood pressure and fluid balance may play an integral role. The renin angiotensin system (RAS), which modulates autonomic nervous system activity and cardiovascular function, also influences learning processes such as fear memory formation and maintenance. Pharmacologically targeting the RAS may be effective in reducing symptoms of fear and anxiety disorders. This dissertation seeks to improve our understanding of the relationship between fear memory and cardiovascular reactivity, as well as the involvement of the RAS in fear learning processes. The first study examines the effects of extinction learning on cardiovascular responses to conditioned auditory stimuli. Through simultaneous recording of freezing behavior, blood pressure, and heart rate, it is shown that blood pressure responses are attenuated by repeated conditioned stimulus exposure. In the second study, the role of the angiotensin II type 1 receptor (AT1R) in the reconsolidation of auditory fear memory is investigated. Our findings suggest that blockade of AT1R during reconsolidation leads to long-term reductions in freezing behavior. Results from this study also indicate that treatment with the AT1R antagonist losartan following memory retrieval leads to differential gene expression patterns in the amygdala. The final study identifies the functional properties of central angiotensin II type 2 receptors (AT2R) in fear expression and extinction. The regional distribution and characteristics of AT2R+ cells within the amygdala are examined in detail. Furthermore, pharmacological activation of AT2R in the central amygdala was used to determine how these receptors might contribute to fear learning and expression. Finally, AT2R-expressing neurons in the central amygdala are shown to project to the periaqueductal grey, a brain region responsible for mediating freezing behavior.The studies in this dissertation are the first to incorporate acute cardiovascular responses such as blood pressure into the assessment of extinction and reconsolidation, which are important clinical targets for the treatment of anxiety and fear. Furthermore, evidence is provided that AT1R contributes to the reconsolidation of auditory fear memories, and that AT2R-expressing neurons in the central amygdala modulate fear expression and extinction. These findings advance our understanding of the physiological and neurobiological systems that regulate fear learning, and suggest that compounds targeting the RAS may be useful in the treatment of fear-related psychiatric conditions.
- All rights reserved
Notice to Authors
If you are the author of this work and you have any questions about the information on this page, please use the Contact form to get in touch with us.