Antiaggressive Effects of Zolpidem and Zopiclone in Agonistic Encounters Between Male Mice

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. © 2002 Wiley‐Liss, Inc.