Stimulus effects of morphine in the monkey: quantitative analysis of antagonism

The ability of narcotic antagonists to block the discriminative stimulus effects of 3.0 mg/kg (IM) of morphine was evaluated quantitatively in the squirrel monkey using a two-choice discrete-trial avoidance paradigm. The time-course and relative potency of naloxone and naltrexone for antagonizing morphine's stimulus effects in the squirrel monkey was similar to those determined in rats and pigeons. Complete blockade of morphine's effects was attained with 0.03 mg/kg of either antagonist when given simultaneously with morphine, but only naltrexone completely blocked the stimulus effects of morphine when the pretreatment interval was extended to 12 and 18 hr. A Schild plot derived from the degree of antagonism of graded doses of morphine by graded doses of naltrexone (0.003-0.1 mg/kg) yielded a line with a slope of -0.63 +/- 0.2 and an apparent pA2 value of 8.25 +/- 0.2. These results demonstrate the feasibility of quantitatively assessing the drug-receptor interactions that subserve the discriminative stimulus effects of morphine in the squirrel monkey.