KAPPA-OPIOID AGONISTS PRODUCE ANXIOLYTIC-LIKE BEHAVIOR ON THE ELEVATED PLUS-MAZE

The selective kappa agonist U-50,488H was evaluated on the elevated pl us-maze test of anxiety. U-50,488H was administered intraperitoneally to male Sprague-Dawley rats 20 min before testing, first in an open fi eld apparatus, then followed immediately on the elevated plus-maze. No significant change in spontaneous locomotor activity was measured in the open held apparatus, suggesting that U-50,488H was devoid of sedat ive effects in the dose range tested (0.1-1000 mu g/kg, IF). Doses bet ween 10 and 1000 mu g/kg produced significant increases in elevated pl us-maze behavior that were consistent with anxiolytic actions for U-50 ,488H. These anxiolytic-like effects were antagonized by naloxone (2.0 mg/kg, IF), suggesting an opioid receptor site of action. In addition , we tested the kappa(1)-selective U-50,488H-derivative, U-69,593 (100 mu g/kg, IF), which was also shown to mimic the anxiolytic-like effec ts 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 a nxiolytic properties in rodents and that the kappa opioid system may b e involved in the behavioral response to anxiety.