Paliperidone suppresses the development of the aggressive phenotype in a developmentally sensitive animal model of escalated aggression.
BACKGROUND
Atypical antipsychotics are commonly prescribed to clinically referred youngsters for treatment of heightened aggressive behavior associated with various psychiatric disorders. Previously, we demonstrated risperidone's anti-aggressive effects using a well-validated animal model of offensive aggression. Paliperidone, the main active metabolite of risperidone, is a potent serotonin-2A and dopamine-2 receptor antagonist with slightly different pharmacodynamic properties compared to risperidone. Given that much of risperidone's therapeutic efficacy is due to its active metabolite, paliperidone may effectively suppress aggression with fewer adverse side effects.


OBJECTIVE
Investigate whether paliperidone administration would reduce heightened aggressive behavior induced by low-dose cocaine exposure in a developmentally sensitive model of offensive aggression.


METHODS
Male Syrian hamsters (n = 12/group) were administered an acute dose of paliperidone (0.05, 0.1, 0.2, and 0.3 mg/kg) and then tested for aggressive behavior using the resident-intruder paradigm. To investigate the effects of chronic paliperidone administration, a separate set of animals (n = 12/group) was exposed to repeated paliperidone administration (0.1 mg kg(-1) day(-1)) during different developmental periods and varying lengths of time (1-4 weeks).


RESULTS
Experiment 1 results revealed a dose-dependent decrease in bite and attack behaviors with an effective dose observed at 0.1 mg/kg. In Experiment 2, the maximal reduction in aggressive behavior in response to chronic paliperidone treatment was observed in animals treated during the third week of adolescence, and this reduction occurred without concomitant alterations in non-aggressive behaviors.


CONCLUSIONS
These results support the specific aggression-suppressing properties of paliperidone and the potential use of this compound in the treatment of maladaptive aggression in clinical settings.
Schwartzer
Jared J
JJ
Behavioral Neuroscience Program, Department of Psychology, 125 Nightingale Hall, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Morrison
Randall L
RL
Ricci
Lesley A
LA
Melloni
Richard H
RH
D000367:Age Factors; D000374:Aggression / Q000187:drug effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D000068882:Paliperidone Palmitate; D010641:Phenotype; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D003042:Cocaine; D000068882:Paliperidone Palmitate