Discriminative stimulus properties of nalorphine in the rhesus monkeys

The discriminative stimulus properties of nalorphine were studied in rhesus monkeys trained to discriminate i.m. injections of nalorphine (1 mg/kg) from saline. During training, a two-lever paradigm was employed where a single, 3-min extinction schedule was followed by fixed-ratio-20 schedules of food presentation. During the fixed-rate schedules, responses on one of the two levers produced food when nalorphine had been administered and responses on the other lever produced food when saline had been administered. During stimulus generalization tests, responses on either lever produced food under the fixed-ratio schedule. The discriminative stimulus effects of nalorphine were antagonized by naloxone which, by itself, did not generalize to nalorphine. The kappa opiate agonists, ethylketocyclazocine, U-50,488, bremazocine, tifluadom, as well as two mixed kappa-sigma agonists, dl-cyclazocine and dl-N-allylnormetazocine (SKF-10047), generalized to nalorphine with the following potency ranking order: bremazocine greater than ethylketocyclazocine greater than tifluadom greater than cyclazocine greater than U-50,488 greater than N-allylnormetazocine greater than nalorphine. The levo-isomers of cyclazocine, N-allylnormetazocine or U-50,488 generalized to nalorphine whereas the dextroisomers did not. Generalization to nalorphine did not occur with the mu opiate agonists, morphine, methadone and meperidine, or the nonopiate compounds, phencyclidine, ketamine and chlorpromazine. The results suggest that a kappa opiate receptor mechanism mediates the discriminative effects of nalorphine in the rhesus monkey, which may also be involved with the naloxone-sensitive, sedative and dysphoric effects of nalorphine in humans.