Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze.

The selective kappa agonist U-50,488H was evaluated on the elevated plus-maze test of anxiety. U-50,488H was administered intraperitoneally to male Sprague-Dawley rats 20 min before testing, first in an open field apparatus, then followed immediately on the elevated plus-maze. No significant change in spontaneous locomotor activity was measured in the open field apparatus, suggesting that U-50,488H was devoid of sedative effects in the dose range tested (0.1-1000 micrograms/kg, IP). Doses between 10 and 1000 micrograms/kg produced significant increases in elevated plus-maze behavior that were consistent with anxiolytic actions for U-50,488H. These anxiolytic-like effects were antagonized by naloxone (2.0 mg/kg, IP), suggesting an opioid receptor site of action. In addition, we tested the kappa 1-selective U-50,488H-derivative, U-69,593 (100 micrograms/kg, IP), which was also shown to mimic the anxiolytic-like effects produced by U-50,488H. These results suggest that low doses of the selective kappa 1 agonists U-50,488H and U-69,593 are endowed with anxiolytic properties in rodents and that the kappa opioid system may be involved in the behavioral response to anxiety.