Infralimbic and dorsal raphe microinjection of the 5-HT sub(1B) receptor agonist CP-93,129: attenuation of aggressive behavior in CFW male mice

Rationale: Aggressive behavior and impaired impulse control have been associated with dysregulations in the serotonergic system and with impaired functioning of the prefrontal cortex. 5-HT sub(1B) receptors have been shown to specifically modulate several types of offensive aggression. Objective: This study aims to characterize the relative importance of two populations of 5-HT sub(1B) receptors in the dorsal raphe nucleus (DRN) and infralimbic cortex (ILC) in the modulation of aggressive behavior. Methods: 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-HT sub(1B) agonist, CP-93,129 (0-1.0 mu g/infusion). Results: In both the DRN and ILC, CP-93,129 reduced aggressive behaviors after both water and alcohol self-administration. Intra-raphe 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. Conclusions: These findings highlight the importance of the serotonergic system in the modulation of aggression and suggest that the behaviorally specific effects of 5-HT sub(1B) receptor agonists are regionally selective. 5-HT sub(1B) 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.