Antinociceptive effects of the kappa opioid, U50,488: lack of modulation by 5-HT2 antagonists.

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