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The effects of benzodiazepines on various types of aggression have been extensively studied. These substances produce their pharmacological effects by allosterically modulating the action of GABA via specific recognition sites on the GABA A receptor called omega 1 and omega 2. The antiaggressive profile of non-benzodiazepine compounds that also act at omega sites, such as zopiclone (a non-selective omega 1 and 2 ligand) and zolpidem (a selective omega 1 ligand) has been scarcely explored. In this study, we examined the action of zolpidem (0.75-3 mg/kg, intraperitoneally) and zopiclone (1.5-6 mg/ kg), administered acutely or subchronically for 10 days, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic ''standard opponents'' 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Acute treatment with zopiclone produced a marked antiaggressive effect, reducing offensive behaviors (threat and attack) at all doses used (1.5, 3, and 6 mg/kg) without affecting immobility. Likewise, the intermediate dose of zolpidem (1.5 mg/kg) significantly decreased aggression in a specific manner, without altering immobility, whereas the highest dose (3 mg/kg) provoked a reduction of aggression accompanied by a weak (but significant) increase of immobility. With repeated treatment, no tolerance to the antiaggressive effects of zopiclone and zolpidem was developed. It is concluded that omega sites at the GABA A receptor could be involved in the control of aggression. Aggr. Behav. 28:416-425, 2002. r

Topiramate, an antiepileptic drug, has been found to be useful for the treatment of aggression in clinical populations. However, no studies have explored the action of this compound on aggressive behavior in laboratory animals. This work examined the effects of topiramate (10, 20, 40 and 80 mg/kg, i.p.) on agonistic interactions between male mice, using an ethopharmacological approach. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration. Ten minutes of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. The encounters were videotaped and the accumulated time allocated by subjects to 10 broad behavioral categories was estimated using an ethologically based analysis. Results showed that topiramate (20-80 mg/kg) produced a significant reduction of offensive behaviors (threat and attack), without affecting immobility. Digging behavior (all doses) was also significantly decreased. The antiaggressive effects of topiramate could be related to its ability for modulating positively GABA-A receptors and/or blocking AMPA subtype of glutamate receptors.

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