Individual susceptibility or resistance to posttraumatic stress disorder-like behaviours

Behav Brain Res. 2020 May 27:386:112591. doi: 10.1016/j.bbr.2020.112591. Epub 2020 Mar 16.

Abstract

The aim of this study was to explore the neurobiological background of individual susceptibility and resistance to the development of posttraumatic stress disorder (PTSD)-like behaviours. Rats were divided into susceptible, PTSD(+), and resistant, PTSD(-), groups based on freezing duration during exposure to aversive context and the time spent in the central area in open field test one week after threefold stress experience (modified single prolonged stress). PTSD(-) rats showed increased concentrations of corticosterone in plasma and changes in GAD67 expression: decreased in the infralimbic cortex (IL) and increased in the lateral amygdala (LA), dentate gyrus (DG), and CA1 area of the hippocampus. Moreover, in this group, we found an increase in the number of CRF-positive nuclei in the parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN). The PTSD(+) group, compared to PTSD(-) rats, had decreased concentrations of corticosterone in plasma and reduced CRF expression in the pPVN, higher CRF expression in the CA1, increased expression of CRF-positive nuclei and GR receptors in the CA3 area of the hippocampus, and increased expression of GR receptors in the DG and the central amygdala (CeA). Biochemical analysis showed higher concentrations of noradrenaline, glutamic acid in the dorsal hippocampus and amygdala and lower levels of dopamine and its metabolites in the amygdala of the PTSD(+) group than in the PTSD(-) group. The study revealed different behavioural and biochemical profiles of PTSD(+) and PTSD(-) rats and suggested that individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity may determine hippocampal- and amygdala-dependent memory and fear processing.

Keywords: Amygdala; Hippocampus; Hypothalamic-pituitary-adrenal axis; Posttraumatic stress disorder; Resistance; Susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Brain / metabolism
  • Corticosterone / analysis
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / metabolism
  • Dentate Gyrus / metabolism
  • Disease Models, Animal
  • Disease Susceptibility / metabolism*
  • Disease Susceptibility / psychology
  • Fear / physiology
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics
  • Genetic Predisposition to Disease / genetics
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Hippocampus / metabolism
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Memory
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Pituitary-Adrenal System / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Wistar
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / metabolism
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Stress, Psychological / physiopathology*

Substances

  • Proto-Oncogene Proteins c-fos
  • Corticotropin-Releasing Hormone
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Corticosterone