Modulation of anxiety-related behaviors by mu- and kappa-opioid receptor agonists depends on the social status of mice.

This study was aimed to determine the effects of mu- and kappa-opioid receptor activation in relation to the social status of mice, being a winner with repeated experience of victories or a loser with repeated experience of social defeats. The behaviors of the animals were assessed in a social encounter test measuring the communicative behavior towards a familiar and an unfamiliar partner behind a perforated transparent partition (partition test) and in an elevated plus-maze test estimating the anxiety level of mice. Placebo and graded doses of the mu-opioid receptor agonist DAMGO (0.5 and 2 mg/kg s.c.) and the kappa-opioid receptor agonist U-50,488H (0.6, 1.25, and 2.5 mg/kg s.c.) were administered to the control mice, winners and losers in two experiments. In the partition test, the winners spent somewhat more time and the losers less time than the controls in the vicinity of their partner probably related to a lower and higher level of anxiety respectively. In the plus-maze test the losers appeared to have a somewhat higher anxiety level than the controls and winners. In both tests DAMGO produced anxiogenic-like effects in the winners and the controls, but not in the losers. Winners hardly responded to treatment with U-50,488H, while the losers responded dose dependently with an anxiolytic-like effect in both tests. It is concluded that anxiety-like responses in mice are differentially affected by stimulation of mu- and kappa-opioid receptors and that the effects depend on the social status of the animals.