Effects of SB-205384, a positive modulator of α3-subunit-containing GABA-A receptors, on isolation-induced aggression in male mice

inhibitory transmission in the mammalian central nervous system. GABA-A receptor belongs to the super-family of ligand-gated ion channels. It is assembled as a pentameric complex (i.e. composed of five subunits), arranged symmetrically to enclose the transmembrane chloride ion channel. Each subunit of GABA-A receptors consists of four trans-membrane domain (TM1-4) modulating the receptor activity. To date, eight subclasses of GABA-A receptor subunits have been cloned in the CNS (α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3) (Steiger & Russek, 2004; Korpi & Sinkkonen, 2006; Rudolph & Möhler, 2006). GABAergic system is clearly involved in the modulation of aggression. Thus, many substances that act on the GABA-A receptors provoke marked effects on aggressive behaviour (Beltrán & Navarro, 2002; Miczek et al., 2002; De Almeida et al., 2005). Drugs with a high affinity for GABA-A receptors which contain the α1 subunit, such as zolpidem, exhibit antiaggressive effects in isolated male mice, suggesting a role for these receptors in the modulation of aggression (Martín-López & Navarro, 2002). Likewise, selective ligands for α5-GABA-A receptors also reduce significantly aggression, although this action seems to be unselective (Navarro et al., 2004). To date, there have been few functional studies involving the α3-GABA-A receptors and, to our knowledge, no studies have focused on the possible role of these receptors in aggression. SB-205384 is an α3 subunit positive modulator of GABA-A receptors. This substance belongs to the group of benzothiophene compounds that act as allosteric modulators of GABA-A receptor function (Meadows et al., 1998). The aim of this study was to examine the role of α3-containing GABA-A receptors in Effects of SB-205384, a positive modulator of α3-subunit-containing GABA-A receptors, on isolation-induced aggression in male mice