Discriminative stimulus effects of cyclorphan: selective antagonism with naltrexone

The opioid antagonist, naltrexone, was used to identify some of the receptor mechanisms responsible for the discriminative stimulus effects of cyclorphan in the pigeon. Subjects were trained to discriminate 10 mg/kg IM injections of either morphine or dextrorphan from saline injections in a two key drug discrimination procedure in which responding was maintained by food presentation. The dextrorphan-trained birds generalized to l-cyclorphan at 10 mg/kg; naltrexone did not alter the l-cyclorphan dose-response curve for this effect. In the morphine-trained group, l-cyclorphan produced only partial generalization, and naltrexone greatly increased the dose of l-cyclorphan necessary to produce this effect. These results are consistent with the conclusion that in morphine-trained pigeons the partial generalization to l-cyclorphan is mediated by opioid receptors. Moreover, limited intrinsic efficacy at mu opioid receptors may be the characteristic of l-cyclorphan that prevents full generalization in morphine-trained pigeons. d-Cyclorphan produced partial generalization in both groups, but the involvement of opioid receptor mechanisms could not be confirmed, as 1 mg/kg naltrexone did not antagonize d-cyclorphan in either group.