5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice.
BACKGROUND
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.
Laboratório de Neurociências, Universidade do Vale do Rio dos Sinos, UNISINOS, São Leopoldo, RS, Brazil.
R M M
RM
De Almeida
M M
MM
Rosa
D M
DM
Santos
D M
DM
Saft
Q
Q
Benini
K A
KA
Miczek
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000502:physiology; D008297:Male; D051379:Mice; D008845:Microinjections; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
C097067:CP 94253; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090701:GR 127935