Stressor controllability and Fos expression in stress regulatory regions in mice

Physiol Behav. 2009 Jun 22;97(3-4):321-6. doi: 10.1016/j.physbeh.2009.02.038. Epub 2009 Mar 9.


Controllability is an important determinant of the effects of stress on behavior. We trained mice with escapable (ES) and inescapable (IS) shock and examined behavioral freezing and Fos expression in brain regions involved in stress to determine whether stressor controllability produced differential activation of these regions. Mice (C57BL/6J) were trained to escape footshock by moving to a safe chamber in a shuttlebox. This terminated shock for both ES mice (n=5) and yoked-control mice receiving IS (n=5). Handling control (HC) mice (n=5) experienced the shuttlebox, but never received footshock. Training took place on three days (20 trials per day, 0.2 mA, 5.0 s maximum duration, 1.0 min interstimulus interval). On day 3, the animals were killed 2 h after training and the brains were processed for Fos expression in the amygdala, hypothalamic paraventricular nucleus (PVN), laterodorsal tegmental nucleus, locus coeruleus and dorsal raphe nucleus. Fos expression after IS was greater than after ES and HC in all regions (p<.05). Fos expression after ES was greater than HC only in PVN (p<.05). Freezing in ES mice was equal to or greater than in IS mice whereas HC mice showed minimal freezing. Differential activation of brain regions implicated in stress may, in part, account for differences in behavior in the aftermath of uncontrollable and controllable stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Brain / metabolism*
  • Electroshock / adverse effects
  • Escape Reaction / physiology*
  • Freezing Reaction, Cataleptic / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology
  • Stress, Psychological / physiopathology


  • Proto-Oncogene Proteins c-fos