, Volume 182, Issue 1, pp 116–127

Escalated aggression as a reward: corticosterone and GABAA receptor positive modulators in mice

  • Eric W. Fish
  • Joseph F. DeBold
  • Klaus A. Miczek
Original Investigation



Individuals seek out the opportunity to fight, but the mechanisms behind this positively reinforcing effect of aggression have yet to be understood.


The aims of this study were to (1) describe behavioral and corticosterone elevations that occur in aggressive mice conditioned to respond for the opportunity to fight another mouse, (2) determine if corticosterone elevations are necessary for operant responding and escalated aggression, and (3) determine if corticosterone elevations alter the aggression-heightening effects of γ-aminobutyric acid (GABA)A receptor positive modulators.

Methods and results

Aggressive male CFW mice were conditioned to respond under the control of a fixed-interval 10-min (FI10) schedule that reinforced their operant behavior by the presentation of an intruder mouse into their home cage. After the FI10, aggressive behavior was ca. 75% higher than the species-typical levels of fighting and plasma corticosterone was more than twice as high after briefly fighting and/or responding on the FI10 schedule. Inhibition of corticosterone synthesis by metyrapone (30–100 mg/kg) reduced both conditioned responding as well as the aggressive behavior after the FI. Although the benzodiazepine midazolam (0.3–3 mg/kg) heightened species-typical aggressive behavior, it did not increase the high level of aggression engendered by the FI schedule. However, midazolam (0.3 mg/kg) and the neurosteroid allopregnanolone (17 mg/kg) both heightened aggression when given after corticosterone synthesis inhibition by metyrapone (56 mg/kg).


These data suggest that corticosterone elevations are required for responding that is motivated by aggressive behavior and for escalated aggression that follows this responding. Corticosterone elevations also appear to inhibit the aggression heightening effect of GABAA receptor positive modulators.


Benzodiazepines Neurosteroids Alcohol HPA activity Reinforcement schedule Anxiety Intruder 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Eric W. Fish
    • 1
    • 3
    • 4
  • Joseph F. DeBold
    • 1
  • Klaus A. Miczek
    • 1
    • 2
  1. 1.Department of PsychologyTufts UniversityMedfordUSA
  2. 2.Departments of Psychiatry, Pharmacology, and NeuroscienceTufts UniversityBostonUSA
  3. 3.Department of Neuroscience, Douglas Hospital Research CentreMcGill UniversityMontrealCanada
  4. 4.Department of NeuroscienceDouglas Hospital Research CentreMontrealCanada

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