Neural background of glucocorticoid dysfunction-induced abnormal aggression in rats: involvement of fear- and stress-related structures

Eur J Neurosci. 2002 Feb;15(3):561-9. doi: 10.1046/j.0953-816x.2001.01883.x.


Glucocorticoid hypofunction is associated with persistent aggression in some psychologically disordered human subjects and, as reported recently, induces abnormal forms of aggression in rats. Here we report on the effects of glucocorticoid hypofunction on aggression-induced neural activation. Rats were adrenalectomized, and implanted with low-release glucocorticoid pellets. After one week recovery, they were challenged by an unfamiliar intruder in their home-cage. Neural activation was studied by c-Fos protein immunocytochemistry. Aggressive encounters in controls induced c-Fos activation in all brain areas relevant for the control of aggression (cortex, amygdala, septum, hypothalamus, periaqueductal grey and the locus coeruleus). Very intense c-Fos activation was observed in the medial amygdala, the hypothalamic attack area and the periaqueductal grey matter which constitute a downward stimulatory stream that activates attack behaviour. The experimentally induced glucocorticoid hypofunction dramatically increased attacks targeted towards vulnerable parts of the opponent's body (mainly the head). This abnormal behaviour was not associated with changes in the activation of brain centres involved in the control of aggression. However, the activation of brain centres involved in both the stress response (the parvocellular part of the hypothalamic paraventricular nucleus) and fear reactions (central amygdala) were markedly increased. An acute glucocorticoid treatment abolished both behavioural and neural consequences of glucocorticoid hypofunction. Our data suggest that glucocorticoid hypofunction-induced abnormal forms of aggressiveness are related to increased sensitivity to stressors and fear-eliciting stimuli. This assumption is supported by the finding that fearful situations induce attack patterns in intact rats that are similar to those induced by glucocorticoid hypofunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy / adverse effects
  • Aggression / drug effects
  • Aggression / physiology*
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Fear / drug effects
  • Fear / physiology*
  • Glucocorticoids / deficiency*
  • Glucocorticoids / pharmacology
  • Limbic System / drug effects
  • Limbic System / metabolism*
  • Limbic System / physiopathology
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Stress, Physiological / physiopathology


  • Glucocorticoids
  • Proto-Oncogene Proteins c-fos