Blockade by narcotic drugs of naloxone-precipitated jumping in morphine-dependent mice

Abstract

A dose regimen for administration of morphine, test drugs with potential to cause physical dependence and naloxone was determined to allow within one experimental day acquisition of morphine-dependent mice and evaluation of the narcotic drugs for their ability to prevent naloxone-precipitated jumping. This test procedure can be used to assess capacity of unknown drugs to suppress morphine withdrawal symptoms; the mechanism of suppression can be subsequently determined in secondary tests. However, for known morphine-like analgesics, the test procedure appears to reliably assess physical dependence properties. The results obtained on subcutaneous administration of five selected narcotic drugs and apomorphine show that their order of potency was methadone greater than meperidine equal apomorphine greater than d-propoxyphene greater than pentazocine. Codeine, also tested subcutaneously, did not substitute at sublethal doses. Except for apomorphine, which might have masked naloxone-precipitated jumping by inducing behavioral aggression, the order of potency compares favorably with the degree of physical dependence reported in humans. Thus, the described procedure might be employed to evaluate morphine substitution and hence potential physical dependence liability of unknown narcotic-like analgesics.