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

Abstract

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

Benzodiazepines and heightened aggressive behavior in rats: reduction by GABAA/?1 receptor antagonists

“…Individual differences in the aggression-heightening effects of alcohol, another positive modulator of the GABA A receptor, are well documented (e.g., Miczek and Barry 1977;Blanchard et al 1987;Lister and Hilakivi 1988;Miczek et al 1992;van Erp and Miczek 1997;Miczek et al 1998;Fish et al 2001). Several BZs do not exert aggression-heightening effects at all: even at low doses, oxazepam, clorazepam, and zolpidem consistently produce anti-aggressive effects (Bond and Lader 1988;Martin-Lopez and Navarro 2002;de Almeida et al 2004), and triazolam fails to increase aggressive behavior in various experimental protocols (Cherek et al 1991;Kruk 1991;de Almeida et al 2004).…”

Estudio de la instigación social en un modelo de agresión inducida por aislamiento: efectos de la administración de JNJ16259685, un antagonista de receptores mGlu1

“…Además de la serotonina, otros sistemas de neurotransmisión han sido implicados en la regulación de la agresión como el GABA (Martín-López & Navarro, 2002 y el glutamato (Navarro, De Castro & Martín-López, 2010), entre otros. El glutamato es el principal neurotransmisor excitador del sistema nervioso central y actúa sobre sus receptores ionotrópicos postsinápticos (NMDA, AMPA y kainato) y sobre los receptores metabotrópicos (mGlu) que modulan su liberación, la respuesta postsináptica y la actividad de otras sinapsis.…”

Effects of LY379268, A Selective Agonist of mGLu2/3 Receptors, on Isolation-Induced Aggression in Male Mice

“…Aggressive behaviour is regulated by a variety of different neurotransmitter systems in the brain, such as serotonine [2,3], dopamine [4,5], GABA [6,7], opiates [8], or gammahydroxybutyrate [9,10]. However, it is now recognized that aggression may be also influenced by glutamate system.…”