Date of Award
Doctor of Philosophy
Dr. Alan Poling
Dr. Lisa Baker
Dr. Jack Michael
Dr. Ennis Berker
Opiate drugs have been classified in two-choice assays according to their ability to produce generalization in animals to the prototypicix opiate, morphine, versus vehicle, or to the k opioid, U -50,488H versus vehicle injections (Picker & Dykstra, 1987). A three-choice discrimination procedure, in which subjects discriminate among morphine, U -50,488H , and vehicle injections, might afford a greater degree of precision in characterizing the subjective effects of opioids. The feasibility of such a procedure was demonstrated in the present study, in which five pigeons were trained to discriminate among injections of 5 .6 m g/kg morphinel 5 .6 m g/kg U -50,488H , and saline. Reliable discrimination was attained by reinforcing injection-appropriate key-pecks under a schedule that required 2 0 consecutive responses on the injection-appropriate key. Orderly dose-response relations were obtained when doses of morphine and U -50,488H from 0.10 to 32.0 m g/kg were substituted for the training doses. Regardless of substitution dose, the subjects almost never responded on the U -50,488H -appropriate key when morphine was administered, or on the morphine-appropriate key when they received U-50,488H.
Pigeons were tested with various doses of naltrexone (0.01 to 1.0 m g/kg) in combination with morphine and U -50,488H in doses ranging from 5.6 to 56 m g/kg. High doses of naltrexone completely blocked the morphine stimulus cue, but failed completely to block the U -50,488H cue. ^/-Amphetamine primarily engendered saline-appropriate, not morphine- or U -50,488H -appropriate, responding. Ethylketazocine produced mixed results in that moderate doses produced responding on both the morphine- and U -50,488H -appropriate keys. How ever, 3.2 m g/kg ethylketa-zocine completely substituted for the morphine cue.
In conclusion, pigeons can be trained to discriminate directly between /x and K opioids. Ethylketazocine, a compound that may be selective for both receptor subtypes, engendered both morphine- and U -50,488H -appropriate responding. Further studies are warranted in other species and with other opioid compounds to evaluate the discriminative stimulus properties of opioids.
Makhay, Malath, "The Discriminative Stimulus Properties of Morphine and U-50,488H in a Three-Key Assay: A MU and Kappa Opioid Discrimination in the Pigeon" (1996). Dissertations. 1720.