Aggressive behavior as a reinforcer in mice: activation by allopregnanolone

Psychopharmacology (Berl). 2002 Oct;163(3-4):459-66. doi: 10.1007/s00213-002-1211-2. Epub 2002 Aug 27.


Rationale: The neurobiological mechanisms that underlie the motivation to engage in an aggressive confrontation remain to be investigated.

Objective: The objective was to develop a method to differentiate pharmacologically the performance elements of aggressive behavior from behaviors that precede an aggressive encounter.

Methods and results: Male CFW mice were housed as "residents" and trained to poke their nose in a hole in a panel placed into the home cage. After fulfilling a specific response requirement, an "intruder" male mouse was introduced for a brief aggressive encounter. In experiment I, the mice were maintained on a fixed ratio schedule of ten responses (FR10) and after stable responding, extinction and stimulus control were assessed by switching the active hole in an ABA design. In experiment II and III, the mice were maintained on a fixed interval schedule of 10 min (FI10 min) and responded with accelerating rates towards the end of the interval (mean index of curvature was 0.37). In experiment III, the mice were given the GABA(A) receptor positive modulator allopregnanolone (5.6-17 mg/kg or vehicle, IP), before responding on an FI10 min schedule reinforced by a 5-min aggressive encounter. Allopregnanolone had bitonic effects on FI responding and aggressive behavior. The low dose of allopregnanolone nearly doubled overall response rate without affecting the index of curvature, attack bites or sideways threats. The moderate dose increased attack behaviors by about 45% and had little effect on response rate and the index of curvature. In contrast, the higher dose decreased the index of curvature but had no effect on aggressive behavior or overall response rate.

Conclusions: These data support previous demonstrations that certain GABA(A) positive modulators heighten aggressive behavior. Moreover, examining operant responding that is reinforced by the opportunity for aggression, it may be possible to dissociate pharmacological effects on the behaviors leading up to an aggressive encounter from their effects on specific aggressive acts.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aggression / drug effects*
  • Animals
  • Behavior, Animal / drug effects*
  • Conditioning, Operant
  • Dose-Response Relationship, Drug
  • Extinction, Psychological
  • Gonadal Steroid Hormones / pharmacology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Pregnanolone / pharmacology*
  • Reinforcement Schedule
  • Reinforcement, Psychology
  • Time Factors


  • Gonadal Steroid Hormones
  • Pregnanolone