The sources of PACAP in the central amygdala in chronic social defeat mice
Embargo Date
2025-02-14
OA Version
Citation
Abstract
Inability to cope with stressful events has been shown to be precipitate or exacerbate several psychopathologies, which include anxiety disorders and post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying the response to chronic stress remain, however, poorly understood. Stress neuropeptides in the extended amygdala mediate the behavioral response to stress, and hyperactivity of these systems may drive the emergence of persistent negative outcomes following the exposure to chronic stress. In this study, we focused on the neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP) and calcitonin gene-related peptide (CGRP), both of which have been proposed to play a key role in stress and pain regulation. We employed the chronic social defeat stress (CSDS) paradigm as a model of chronic psychosocial stress in mice, and then used immunohistochemistry and fluorescence microscopy to examine changes in the levels of these peptides. We found that 10 days of CSDS caused a significant increase in PACAP levels in both the central nucleus of the amygdala (CeA) and the lateral parabrachial nucleus (LPBn) of mice, as well as a decrease of CGRP levels in the LPBn, compared to control, unstressed animals. These findings support the notion that the activation of the PACAP system in the CeA may mediate the behavioral outcomes of chronic psychosocial stress and may therefore represent a target for medication development, while the role of CGRP may be more complex. In addition, to begin investigating the mechanism of action of PACAP in the CeA, we found that PAC1R is co-expressed with PKCĪ“, the marker of a CeA neuronal population that has been shown to mediate aversion, anxiogenesis and nociception, indicating the need for further study of the potential involvement of PKCĪ“ neurons in PAC1R-mediated pathology following CSDS.
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Attribution 4.0 International