DRUG DISCRIMINATION ASSESSMENT OF AGONIST-ANTAGONIST OPIOIDS IN HUMANS - A 3-CHOICE SALINE-HYDROMORPHONE-BUTORPHANOL PROCEDURE

To assess the discriminative stimulus properties of mixed agonist-anta gonist opioids in humans, postaddict volunteers were trained in a thre e-choice drug discrimination procedure to discriminate among the effec ts of saline (4 ml i.m.), hydromorphone (3 mg i.m.) and butorphanol (6 mg i.m.). Subjects earned monetary reinforcement by correctly identif ying the training drugs by letter code. Other subjective, behavioral a nd physiological measures were concurrently collected. After training, generalization curves for hydromorphone, butorphanol, pentazocine, na lbuphine and buprenorphine were determined. In generalization testing, both hydromorphone and butorphanol produced dose-related increases in hydromorphone-appropriate and butorphanol-appropriate responses, resp ectively, and other characteristic subjective effect measures. Nalbuph ine produced dose-related increases in discrimination as butorphanol a nd in those subjective effect measures increased by butorphanol. Bupre norphine produced dose-related increases in discrimination as hydromor phone and in those subjective effect measures increased by hydromorpho ne. Pentazocine was not consistently discriminated as either butorphan ol or hydromorphone. These results differ from those of previous discr imination studies using similar methods but different training drugs. Compared to a previous study in which pentazocine served as the kappa- like training drug, the use as a training drug of the more pharmacolog ically specific kappa-like drug butorphanol permitted greater differen tiation among test drugs and yielded discrimination results more consi stent with other pharmacological evidence (buprenorphine being mu-like and nalbuphine being kappa-like). There was a close relationship betw een results of the discrimination measures and the subjective effect m easures.