5-HT1B receptors, ventral orbitofrontal cortex, and aggressive behavior in mice
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Systemic injections of 5-HT1B receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT1B 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.
To assess the anti-aggressive effects of the 5-HT1B receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 μg/0.2 μl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 μg/0.2 μl) in separate groups of aggressive resident male mice. To confirm the 5-HT1B receptor as the critical site of action for the anti-aggressive effects, the 5-HT1B/D antagonist GR-127,935 was microinjected at 10.0 μg/0.2 μl 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.
Microinjections of CP-94,253 (0.56 and 1.0 μg/0.2 μl) 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 μg/0.2 μl) did not have significant behavioral effects.
The results highlight the 5-HT1B receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.