Acute restraint stress regulates brain DNMT3a and promotes defensive behaviors in male rats

Neurosci Lett. 2024 Jan 18:820:137589. doi: 10.1016/j.neulet.2023.137589. Epub 2023 Dec 14.


Depending on its duration and severity, stress may contribute to neuropsychiatric diseases such as depression and anxiety. Studies have shown that stress impacts the hypothalamic-pituitary-adrenal (HPA) axis, but its downstream molecular, behavioral, and nociceptive effects remain unclear. We hypothesized that a 2-hour single exposure to acute restraint stress (ARS) activates the HPA axis and changes DNA methylation, a molecular mechanism involved in the machinery of stress regulation. We further hypothesized that ARS induces anxiety-like and risk assessment behavior and alters nociceptive responses in the rat. We employed biochemical (radioimmunoassay for corticosterone; global DNA methylation by enzyme immunoassay and western blot for DNMT3a expression in the amygdala, ventral hippocampus, and prefrontal cortex) and behavioral (elevated plus maze and dark-light box for anxiety and hot plate test for nociception) tests in adult male Wistar rats exposed to ARS or handling (control). All analyses were performed 24 h after ARS or handling. We found that ARS increased corticosterone levels in the blood, increased the expression of DNMT3a in the prefrontal cortex, promoted anxiety-like and risk assessment behaviors in the elevated plus maze, and increased the nociceptive threshold observed in the hot plate test. Our findings suggest that ARS might be a helpful rat model for studying acute stress and its effects on physiology, epigenetic machinery, and behavior.

Keywords: Acute restraint stress; Anxiety-like behaviors; DNA methylation; Prefrontal cortex.

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Brain / metabolism
  • Corticosterone*
  • Hypothalamo-Hypophyseal System* / metabolism
  • Male
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Wistar
  • Restraint, Physical / psychology
  • Stress, Psychological / psychology


  • Corticosterone