title: Escalated aggression as a reward: corticosterone and GABA(A) receptor positive modulators in mice.
abstract: BACKGROUND
  Individuals seek out the opportunity to fight, but the mechanisms behind this positively reinforcing effect of aggression have yet to be understood.
  
  
  OBJECTIVE
  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 gamma-aminobutyric acid (GABA)(A) receptor positive modulators.
  
  
  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).
  
  
  CONCLUSIONS
  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 GABA(A) receptor positive modulators.
authors.affiliation: Department of Psychology, Tufts University, Medford, MA, USA. eric.fish@douglas.mcgill.ca
authors.forename: Eric W
authors.initials: EW
authors.lastname: Fish
authors.forename: Joseph F
authors.initials: JF
authors.lastname: DeBold
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000374:Aggression / Q000187:drug effects*; D000378:Agonistic Behavior / Q000187:drug effects*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008874:Midazolam / Q000494:pharmacology; D012201:Reward; D013045:Species Specificity
chemical_list: D058785:GABA-A Receptor Agonists; D008874:Midazolam; D003345:Corticosterone; D008797:Metyrapone