Antagonism of the analgesic effects of mu and kappa opioid agonists in the squirrel monkey

Abstract

The effects of several mu and kappa opioid agonists were examined alone and in combination with the opioid antagonist quadazocine in squirrel monkeys responding under a schedule of shock titration. Under this procedure, shock was scheduled to increase once every 15 sec from 0.01 to 2.0 mA in 30 steps. Five responses on a lever during the 15-sec shock period terminated the shock for 15 sec, after which the shock resumed at the next lower intensity. The intensity below which the monkeys maintained the shock 50% of the time (median shock level) and the rate of responding in the presence of shock were determined under control conditions and after administration of the mu agonists, l-methadone and fentanyl and the kappa agonists, bremazocine, ethylketocyclazocine, ketocyclazocine and U50,488. When examined alone, intermediate doses of mu and kappa agonists increased median shock level. At the highest doses of these compounds responding was eliminated and shock rose to its peak intensity. When the mu and kappa agonists were examined in combination with quadazocine, dose-effect curves for median shock level and for rate of responding were shifted to the right in a dose-dependent fashion. A comparison of the pA2 values for quadazocine on median shock level and on rate of responding revealed similar values for the two measures; however, pA2 values differed depending on the agonist examined. That is, the pA2 values for quadazocine in combination with l-methadone and fentanyl on median shock level were 7.43 and 7.61, respectively; whereas the pA2 value for quadazocine in combination with bremazocine and U50,488 were 6.53 and 6.43, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)