Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT(1B) receptor agonist CP-94,253

Psychopharmacology (Berl). 1999 Oct;146(4):391-9. doi: 10.1007/pl00005484.


Rationale: Models of heightened aggression may be particularly relevant in exploring pharmacological options for the clinical treatment of aggressive and impulsive disorders.

Objectives: To investigate and compare the effects of a 5-HT(1B) selective agonist, CP-94,253, on aggression that was heightened as a result of 1) social instigation or 2) alcohol treatment.

Methods: Male CFW mice were administered 1.0 g/kg EtOH and were subsequently confronted by an intruder in their home cage. In a separate experimental procedure, resident male mice were instigated to aggressive behavior by brief exposure to a provocative stimulus male. To test the hypothesis that activation of the 5-HT(1B )receptor subtype would preferentially attenuate heightened aggression, in comparison to the moderate levels of species-typical aggressive behaviors, the selective agonist, CP-94,253 (1.0-30 mg/kg, IP), and antagonists to the 5-HT(1B) (GR 127935; 10 mg/kg, IP) and the 5-HT(1A) receptor (WAY 100,635; 0.1 mg/kg IP) were used.

Results: CP-94,253 suppressed non-heightened aggressive behavior (ED(50)=7.2 mg/kg ). GR 127935, but not WAY 100,635 shifted the ED(50) for CP-94,253 to 14.5 mg/kg. Importantly, the anti-aggressive effects of CP-94,253 were not accompanied by locomotor sedation. Alcohol-heightened and instigation-heightened aggression were suppressed at lower doses than those necessary to suppress non-heightened aggression (ED(50)=3. 8 and 2.7 mg/kg, respectively).

Conclusions: The current results support the hypothesis that activation of 5-HT(1B) receptors modulates very high levels of aggressive behavior in a pharmacologically and behaviorally specific manner.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aggression / drug effects*
  • Animals
  • Behavior, Animal / drug effects
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / pharmacology*
  • Male
  • Mice
  • Oxadiazoles / pharmacology
  • Piperazines / pharmacology
  • Pyridines / pharmacology*
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*


  • CP 94253
  • Central Nervous System Depressants
  • Oxadiazoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • GR 127935
  • Ethanol