Behavioral profile of L-655,708, a selective ligand for the benzodiazepine site of GABA-A receptors which contain the α5 subunit, in social encounters between male mice

GABA-A receptor is a transmembrane hetero-oligomeric protein which consists of five subunits, the combination of which confers unique pharmacological properties to the receptor. It is well-known that the GABAergic system is involved in the modulation of aggression. However, the role of alpha5/GABA-A receptors has not been explored. In this study, we examined the effect of L-655,708 (0.625-5 mg/kg), a selective ligand for the benzodiazepine site of CABA-A receptors which contain the alpha5 subunit, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to an anosmic "standard opponent" 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. L-655,708 (5 mg/kg) exhibited an ethopharmacological profile characterized by a marked reduction of the time spent in offensive behavior (threat and attack) without affecting immobility, accompanied by a significant increase of avoidance/flee and nonsocial exploration behaviors, suggesting that the antiaggressive effect of the drug is unselective. Overall, this behavioral profile might indicate the existence of an anxiogenic-like activity of L-655,708 in mice. (C) 2004 Wiley-Liss, Inc.