Social agonistic distress in male and female mice: changes of behavior and brain monoamine functioning in relation to acute and chronic challenges

PLoS One. 2013;8(4):e60133. doi: 10.1371/journal.pone.0060133. Epub 2013 Apr 2.


Stressful events promote several neuroendocrine and neurotransmitter changes that might contribute to the provocation of psychological and physical pathologies. Perhaps, because of its apparent ecological validity and its simple application, there has been increasing use of social defeat (resident-intruder) paradigms as a stressor. The frequency of stress-related psychopathology is much greater in females than in males, but the typical resident-intruder paradigm is less useful in assessing stressor effects in females. An alternative, but infrequently used procedure in females involves exposing a mouse to a lactating dam, resulting in threatening gestures being expressed by the resident. In the present investigation we demonstrated the utility of this paradigm, showing that the standard resident-intruder paradigm in males and the modified version in females promoted elevated anxiety in a plus-maze test. The behavioral effects that reflected anxiety were more pronounced 2 weeks after the stressor treatment than they were 2 hr afterward, possibly reflecting the abatement of the stress-related of hyper-arousal. These treatments, like a stressor comprising physical restraint, increased plasma corticosterone and elicited variations of norepinephrine and serotonin levels and turnover within the prefrontal cortex, hippocampus and central amygdala. Moreover, the stressor effects were exaggerated among mice that had been exposed to a chronic or subchronic-intermittent regimen of unpredictable stressors. Indeed, some of the monoamine changes were more pronounced in females than in males, although it is less certain whether this represented compensatory changes to deal with chronic stressors that could result in excessive strain on biological systems (allostatic overload).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Anxiety / metabolism
  • Behavior, Animal*
  • Brain / metabolism*
  • Corticosterone / blood
  • Female
  • Hippocampus / metabolism
  • Male
  • Maze Learning
  • Mice
  • Norepinephrine / metabolism
  • Prefrontal Cortex / metabolism
  • Serotonin / metabolism
  • Stress, Psychological / blood
  • Stress, Psychological / metabolism*
  • Stress, Psychological / therapy


  • Serotonin
  • Corticosterone
  • Norepinephrine

Grant support

The research was supported by the Natural Sciences and Engineering Research Council of Canada. HA holds a Canada Research Chair in Neuroscience. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.