Effects of (+)SKF 10047, a sigma-1 selective agonist, on isolation-induced aggression in male mice.

sigma-1 Receptors have been identified in numerous brain regions, including areas such as hypothalamus and amygdala, which have long been linked to the regulation of aggression. However, there is no clear information with respect to the possible effects of sigma-1 ligands on aggressive behavior in laboratory animals. Consequently, the present study examined the effects of (+)SKF 10047 (0.5-6 mg/kg, i.p.), a sigma-1 prototypical agonist, on isolation-induced aggression in male mice, using an ethopharmacological approach. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration. Ten minutes 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 10 broad behavioral categories was estimated using an ethologically based analysis. Results showed that (+)SKF 10047 (6 mg/kg) produced a significant reduction of offensive behaviors, without affecting immobility. Social investigation behaviors were also slightly increased after drug treatment (2-6 mg/kg). These results suggest a role for sigma-1 receptors in aggression modulation in mice.