Risperidone Exerts Potent Anti-aggressive Effects in a Developmentally Immature Animal Model of Escalated Aggression

Background Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet no information is available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies that use validated developmentally immature animal models of escalated aggression. Previously, we have shown that exposure to low doses of the psychostimulant cocaine-hydrochloride (.5 mg/kg intraperitoneally) during the majority of pubertal development (postnatal days [P]27–57) generates animals that exhibit a high level of offensive aggression. This study examined whether risperidone exerts selective aggression-suppressing effects by using this pharmacologic animal model of highly escalated offensive aggression. Methods Experimental hamsters were tested for offensive aggression after the acute administration of risperidone (.05–1.0 mg/kg, intraperitoneally). Results Risperidone dose-dependently reduced the highly aggressive phenotype, with a significant reduction observed at .1–.2 mg/kg for most aggressive responses measured. Experimental animals treated with higher doses of risperidone (.3–1.0 mg/kg) showed significant reductions in aggression and social interest toward intruders, indicating more general behavioral inhibition. Conclusions These studies provide evidence that risperidone exerts specific aggression-suppressing effects in a developmentally immature animal model of escalated aggression.