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

Abstract

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.

• Authors: R M M De Almeida, M M Rosa, D M Santos, D M Saft, Q Benini, K A Miczek
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 185 Issue 4 Pg. 441-50 (May 2006) ISSN: 0033-3158 [Print] Germany
• PMID: 16550387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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