Infralimbic and dorsal raphé microinjection of the 5-HT1B receptor agonist CP-93,129: attenuation of aggressive behavior in CFW male mice
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- Faccidomo, S., Quadros, I.M.H., Takahashi, A. et al. Psychopharmacology (2012) 222: 117. doi:10.1007/s00213-011-2629-1
Aggressive behavior and impaired impulse control have been associated with dysregulations in the serotonergic system and with impaired functioning of the prefrontal cortex. 5-HT1B receptors have been shown to specifically modulate several types of offensive aggression.
This study aims to characterize the relative importance of two populations of 5-HT1B receptors in the dorsal raphé nucleus (DRN) and infralimbic cortex (ILC) in the modulation of aggressive behavior.
Male CFW mice were conditioned on a fixed-ratio 5 schedule of reinforcement to self-administer a 6% (w/v) alcohol solution. Mice repeatedly engaged in 5-min aggressive confrontations until aggressive behavior stabilized. Next, a cannula was implanted into either the DRN or the ILC. After recovery, mice were tested for aggression after self-administration of either 1.0 g/kg alcohol or water prior to a microinjection of the 5-HT1B agonist, CP-93,129 (0–1.0 μg/infusion).
In both the DRN and ILC, CP-93,129 reduced aggressive behaviors after both water and alcohol self-administration. Intra-raphé CP-93,129 dose-dependently reduced both aggressive and locomotor behaviors. However, the anti-aggressive effects of intra-cortical CP-93,129 were behaviorally specific.
These findings highlight the importance of the serotonergic system in the modulation of aggression and suggest that the behaviorally specific effects of 5-HT1B receptor agonists are regionally selective. 5-HT1B receptors in a medial subregion of the prefrontal cortex, the ILC, appear to be critically involved in the attenuation of species-typical levels of aggression.