Brady L S, Holtzman S G
Pharmacol Biochem Behav. 1981 Mar;14(3):361-70. doi: 10.1016/0091-3057(81)90403-2.
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.
比较了吗啡和纳洛酮对非依赖、吗啡依赖及戒断后大鼠运动活性的影响。通过每6小时定时给予0.05%吗啡溶液10分钟，诱导并维持依赖状态30周。低剂量吗啡可增加非依赖和依赖动物的运动活性，高剂量则使其降低。这两种作用均被纳洛酮拮抗。慢性吗啡处理使动物对高剂量吗啡的抑制作用产生显著耐受性，但对低剂量吗啡的兴奋作用未产生耐受性。戒断后动物仍对高剂量吗啡的抑制作用具有耐受性。依赖及戒断后动物对吗啡抑制作用而非兴奋作用产生耐受性，这表明不同的神经元底物介导了吗啡诱导的运动活性刺激和抑制。突然戒断或纳洛酮诱发的戒断通常会扰乱依赖大鼠的运动活性。单独使用纳洛酮也会降低戒断后动物的活性。因此，慢性吗啡给药会使依赖及戒断后大鼠对吗啡和纳洛酮对运动活性的影响的敏感性产生持久变化。
