The role of the dorsal hippocampus in resistance to the development of posttraumatic stress disorder-like behaviours

Behav Brain Res. 2023 Feb 13:438:114185. doi: 10.1016/j.bbr.2022.114185. Epub 2022 Nov 3.

Abstract

This study aimed to determine the activity of the dorsal hippocampus (dHIP) in resistance to the development of posttraumatic stress disorder (PTSD)-like behaviours. Rats were divided into resistant, PTSD(-), and susceptible, PTSD(+) groups based on the time spent in the central area in an open field test and freezing duration during exposure to an aversive context one week after stress experience (electric foot shock). The PTSD(-) rats, compared to the PTSD(+) group, had an increased concentration of corticosterone in plasma and changes in the activity of the dHIP, specifically, increased c-Fos expression in the dentate gyrus (DG) and increased Neuroligin-2 (marker of GABAergic neurotransmission) expression in the DG and CA3 area of the dHIP. Moreover, in the hippocampus, the PTSD(-) group showed decreased mRNA expression for corticotropin-releasing factor receptors type 1 and 2, increased mRNA expression for orexin receptor type 1, and decreased miR-9 and miR-34c levels compared with the PTSD(+) group. This study may suggest that the increase in GABA signalling in the hippocampus attenuates the activity of the CRF system and enhances the function of the orexin system. Moreover, decreased expression of miR-34c and miR-9 could facilitate fear extinction and diminishes the anxiety response. These effects may lead to an anxiolytic-like effect and improve resistance to developing PTSD-like behaviours.

Keywords: Corticotropin-releasing factor receptors type 1 and 2; GABA; Hippocampus; Posttraumatic stress disorder; Resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents* / pharmacology
  • Extinction, Psychological
  • Fear / physiology
  • Hippocampus / metabolism
  • MicroRNAs* / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Stress Disorders, Post-Traumatic*

Substances

  • Anti-Anxiety Agents
  • RNA, Messenger
  • MicroRNAs
  • MIRN9 microRNA, rat