Quantitation of physical dependence in mice by naloxone-precipitated jumping after a single dose of morphine.

Jumping behavior in mice was precipitated by naloxone after single doses of morphine. The time-effect curves showed that this jumping behavior was delayed compared to the ability of morphine to inhibit writhing and to increase locomotor activity. This dissociation suggests that the jumping response is a true measure of physical dependence rather than the result of a stimulant effect of morphine in the presence of naloxone. The minimum dose of morphine needed to initiate measurable physical dependence fell within the analgesic range. With a constant dose of morphine, the frequency of jumping was directly related to the dose of naloxone employed. The ability to follow the initiation of physical dependence might be useful in conjunction with receptor and neurohumoral studies to uncover the basic mechanisms involved.