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)