Post-traumatic Stress Avoidance Is Attenuated by Corticosterone and Associated With Brain Levels of Steroid Receptor co-activator-1 in Rats

Stress. 2016;19(1):69-77. doi: 10.3109/10253890.2015.1094689. Epub 2015 Oct 20.

Abstract

Individuals with post-traumatic stress disorder (PTSD) avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal (HPA) axis activation at the time of stress. Our rodent model of stress mimics the avoidance symptom cluster of PTSD. Rats are classified as "Avoiders" or "Non-Avoiders" post-stress based on the avoidance of a predator-odor paired context. Previously, we found Avoiders exhibit an attenuated HPA stress response to predator odor. We hypothesized that corticosterone administration before stress would reduce the magnitude and incidence of stress-paired context avoidance. Furthermore, we also predicted that Avoiders would exhibit altered expression of glucocorticoid receptor (GR) signaling machinery elements, including steroid receptor co-activator (SRC)-1. Male Wistar rats (n = 16) were pretreated with corticosterone (25 mg/kg) or saline and exposed to predator-odor stress paired with a context and tested for avoidance 24 h later. A second group of corticosterone-naïve rats (n = 24) were stressed (or not), indexed for avoidance 24 h later, and killed 48 h post-odor exposure to measure phosphorylated GR, FKBP51 and SRC-1 levels in the paraventricular nucleus (PVN), central amygdala (CeA) and ventral hippocampus (VH), all brain sites that highly express GRs and regulate HPA function. Corticosterone pretreatment reduced the magnitude and incidence of avoidance. In Avoiders, predator-odor exposure led to lower SRC-1 expression in the PVN and CeA, and higher SRC-1 expression in the VH. SRC-1 expression in PVN, CeA and VH was predicted by prior avoidance behavior. Hence, a blunted HPA stress response may contribute to stress-induced neuroadaptations in central SRC-1 levels and behavioral dysfunction in Avoider rats.

Keywords: Central amygdala; glucocorticoid receptor; paraventricular nucleus; post-traumatic stress disorder; predator odor; ventral hippocampus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Avoidance Learning / drug effects*
  • Avoidance Learning / physiology
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Brain / metabolism*
  • Corticosterone / pharmacology*
  • Hippocampus / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Nuclear Receptor Coactivator 1 / metabolism*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Pituitary-Adrenal System / physiopathology
  • Rats
  • Rats, Wistar
  • Receptors, Glucocorticoid / metabolism*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Tacrolimus Binding Proteins / metabolism*

Substances

  • NR3C1 protein, rat
  • Receptors, Glucocorticoid
  • Nuclear Receptor Coactivator 1
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5
  • Corticosterone