Enduring Effects Of Traumatic Stress On Brain Neuropeptide Y (NPY) and Corticotropin-Releasing Factor (CRF) Systems: Molecular and Neuropharmacologic Studies

摘要

The funding period allowed us to: 1) further validate repeated social defeat as a model of post-traumatic stress, and 2) demonstrate that the social defeat model is associated with central elevations of CRF levels, as evidenced in CSF samples, as well as a blunted active phase corticosterone- rhythm, neuroendocrine changes that have been described in some patients with PTSD. Moreover, both neurochemical and pharmacological data strongly implicated a role for amygdala Ucn 3-CRF2 systems in the response to social defeat, with intra-amygdala administration of a CRF2 agonist increasing dominance behavior in animals that had experienced social conflict. Data did not indicate strong adaptations in NPY/Y1/Y2 systems of the amygdala or nucleus accumbens in the defeat model. In contrast, novel data also implicated increases in dynorphin- kappa opioid receptor signaling in the nucleus accumbens in responses to social defeat. Further study of the functional significance of the amygdala- CRF2 and nucleus accumbens-kappa opioid receptor system for post-traumatic stress- symptoms is warranted.