Locomotor activity in morphine-dependent and post-dependent rats.

The effects of morphine and naloxone were compared on the locomotor activity of nondependent, morphine-dependent, and post-dependent rats. Dependence was induced and maintained for 30 weeks by scheduled access to 0.05% morphine solution for 10 min every 6 hr. Locomotor activity in nondependent and dependent animals was increased by low doses of morphine and reduced by higher doses. Both components were antagonized by naloxone. Chronic morphine treatment produced marked tolerance to the depressant effect of high morphine doses, but not to the stimulant effect of low doses. Post-dependent animals remained tolerant to the depressant effect of high doses of morphine. The development of tolerance to the depressant but not to the stimulant effect of morphine in dependent and post-dependent animals suggests that different neuronal substrates mediate morphine-induced stimulation and depression of locomotor activity. Abrupt or naloxone-precipitated withdrawal generally disrupted locomotor activity in dependent rats. Naloxone alone also decreased activity in post-dependent animals. Thus, chronic morphine administration produces long-lasting changes in the sensitivity of dependent and post-dependent rats to the effects of morphine and naloxone on locomotor activity.