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

Recent studies indicate that glutamate metabotropic receptors (mGlu) 1 and 5 are involved in the regulation of aggressive behaviour. Brain distribution of mGlu2/3 receptors suggests that they may also play important roles in emotional responses, including aggression. This study examines the effects of LY379268 (0.254 mg/kg, ip), a selective agonist of the mGlu2/3 receptors, on agonistic interactions between male mice using an animal model of isolation-induced aggression. Individually housed mice were exposed to anosmic “standard opponents” 30 min after drug administration. Ten min 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 ten broad behavioural categories was estimated using an ethologically based analysis. LY379268 (2 mg/kg) significantly reduced attack behaviour, as compared with the control group, without affecting immobility, whereas the highest dose of the drug (4 mg/kg) also decreased offensive behaviours (threat and attack), but with a marked increase of immobility (non-selective effect). These results indicate that mGlu2/3 receptors might be implicated in the modulation of aggression.