Study Of The Mechanism Of Aggression--Anti-Aggressive Effect Of Valproate Sodium And Topiramate In Isolated Mice

OBJECT:To study the effects of valproate sodium and topiramate on spontaneous motor activity behavior and isolation-induced aggression in mice, and thus to discuss the mechanism of aggression and provide some evidence for drug treatment.METHODS:Male Kunming mice were isolated for 40~45days as an animal model of isolation-induced aggression. The isolated and group-housed mice were administrated with different doses of valproate sodium(0mg/kg,50mg/kg,100mg/kg,200mg/kg)and topiramate(0mg/kg,25mg/kg,50mg/kg,100mg/kg).The aggressiveness of isolated mice was measured 30min after the administration of valproate sodium or 120 min after the administration of topiramate. The mechanism of aggression was exploreded by joint administration of valproate sodium and topiramate. The spontaneous motor activity in group-housed mice was measured with the apparatus of locomotion for mice (ZIL-2).RESULT:(1) The latencies (±S)to attacking in valproate sodium groups were respectively (4.2±3.3)s,(3.6±1.8)s,(131.0±62.7)s,(261.0±45.1)s. The third and the forth groups were significantly different from the first group (p<0.05), showing it can obviously inhibit aggression in isolated mice ,whereas the second group failed to attenuate aggression. Valproate sodium can also dose-dependently decrease spontaneous motor activity in group-housed mice.(2) The latencies (±S)to attacking in topiramate groups were respectively (28.0±13.0)s, (21.0±.13.4)s ,(75.0±29.9)s, (146.4±42.8)s. The third and the forth groups were significantly different from the first group(p<0.05), showing it can obviously inhibited aggression in isolated mice ,whereas the second group failed to attenuate aggression. The same doses did not affect spontaneous motor activity in group-housed mice.(3)The combination of ineffective doses of valproate sodium and topiramate on aggression prolonged the latency to attacking and antagonized isolation-induced aggression behavior .The combination of the same doses of them did not affect spontaneous motor activity in group-housed mice.CONCLUSION:Both valproate sodium and topiramate are inhibitors of aggression behavior in isolated mice . Topiramate and valproate sodium have synergism .