5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice

Psychopharmacology (Berl). 2006 May;185(4):441-50. doi: 10.1007/s00213-006-0333-3. Epub 2006 Mar 21.


Rationale: Systemic injections of 5-HT(1B) receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT(1B) receptors in the ventral orbitofrontal cortex (VO PFC), an area that has been implicated in the inhibitory control of behavior and is a terminal region for 5-HT projections.

Objective: To assess the anti-aggressive effects of the 5-HT(1B) receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 microg/0.2 microl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 microg/0.2 microl) in separate groups of aggressive resident male mice. To confirm the 5-HT(1B) receptor as the critical site of action for the anti-aggressive effects, the 5-HT(1B/D) antagonist GR-127,935 was microinjected at 10.0 microg/0.2 microl into the VO PFC. After recovery from surgery, the anti-aggressive effects of microinjected CP-94,253 were studied during 5-min resident-intruder confrontations that were recorded and analyzed.

Results: Microinjections of CP-94,253 (0.56 and 1.0 microg/0.2 microl) dose-dependently reduced the frequency of attack bites and sideways threats. This effect was behaviorally specific because non-aggressive motor activities were not significantly altered by the drug. In the IL vmPFC or in an area lateral to the VO PFC, CP-94,253 (1.0 microg/0.2 microl) did not have significant behavioral effects.

Conclusions: The results highlight the 5-HT(1B) receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects*
  • Animals
  • Behavior, Animal / drug effects
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Limbic System / physiology
  • Male
  • Mice
  • Microinjections
  • Oxadiazoles / administration & dosage
  • Oxadiazoles / pharmacology
  • Piperazines / administration & dosage
  • Piperazines / pharmacology
  • Prefrontal Cortex / drug effects*
  • Pyridines / administration & dosage
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1B / drug effects*
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology


  • CP 94253
  • Oxadiazoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • GR 127935