ANTINOCICEPTIVE EFFECTS OF THE KAPPA-OPIOID, U50,488 - LACK OF MODULATION BY 5-HT(2) ANTAGONISTS

The kappa opioid, U50,488, was examined alone and in combination with the 5HT2 antagonists, ketanserin, pirenperone and LY 53857. Squirrel m onkeys responded under a shock titration procedure in which shock inte nsity increased every 15 s from 0.01 to 2.0 mA in 30 steps. Five respo nses terminated the shock for 15 s, after which the shock resumed at t he next lower intensity. The level at which the monkeys kept the shock 50% of the time (median shock level/MSL) was determined. U50,488 alon e produced dose-dependent increases in median shock level whereas none of the 5-HT2 antagonists altered responding under this procedure. Whe n ketanserin (0.032-5.6 mg/kg) was administered in combination with U5 0,488, very high doses of ketanserin (3.2-5.6 mg/kg) shifted the U50,4 88 dose-effect curve to the left. Neither pirenperone (0.032-10.0 mug/ kg) nor LY53857 (0.01-0.32 mg/kg) altered the U50,488 dose-effect curv e in any monkey. Taken together, these data do not support a role for the 5-HT2 system in kappa-induced antinociception in the primate.