Differentiation between mu and kappa receptor-mediated effects in opioid drug discrimination: apparent pA2 analysis

Apparent pA2 values for the opioid antagonist, quadazocine, were used to characterize differential involvement of mu and kappa opioid receptors in the discriminative stimulus effects of opioid agonists. Rhesus monkeys were trained to discriminate s.c. injections of either codeine or ethylketazocine from sham injections. In tests of drug generalization, morphine, levorphanol and alfentanil all produced dose-dependent increases in codeine-appropriate responding, and ethylketazocine produced dose-dependent increases in ethylketazocine-appropriate responding. Quadazocine antagonized the discriminative stimulus effects of each of the agonists. Apparent pA2 values for quadazocine (and slopes of the regression lines fit to the data in "Schild Plot" analysis) were 7.8 (-1.0) with morphine, 7.7 (-1.4) with levorphanol, 7.9 (-0.92) with alfentanil and 5.7 (-0.93) with ethylketazocine. If regression line slopes were constrained to equal -1, 7.8 was the apparent pA2 value with all agonists except ethylketazocine (5.7). This difference in apparent pA2 values for quadazocine confirms that different receptors (mu and kappa, respectively) mediate the discriminative effects of opioid agonists in codeine- and ethylketazocine-trained rhesus monkeys. Also, when the antagonism data were reanalyzed separately for each individual monkey, apparent pA2 values from individual animals were found to be similar to values from other animals in the same group and to values based on grouped data.