title: Aggressive behavior as a reinforcer in mice: activation by allopregnanolone.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Psychology, Tufts University, 530 Boston Ave (Bacon Hall), Medford, MA 02155, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Fish
authors.forename: Joseph F
authors.initials: JF
authors.lastname: De Bold
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D011280:Pregnanolone / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D013997:Time Factors
chemical_list: D012739:Gonadal Steroid Hormones; D011280:Pregnanolone