Opioid physical dependence development in humans: effect of time between agonist pretreatments.
Opioid physical dependence development in humans: effect of time between agonist pretreatments.
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人类阿片类药物身体依赖性的发展：激动剂预处理之间时间的影响。
DOI：
10.1007/bf02244902
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发表时间：
1993
影响因子：
3.4
通讯作者：
Stitzer,ML
中科院分区：
文献类型：
--
作者：
Kirby,KC;Stitzer,ML
我们研究了吗啡预处理间隔对随后的催促戒断反应强度的影响，以检验戒断强度与预处理间隔呈负相关的假设。受试者是10名非依赖性男性志愿者，他们报告平均每周使用阿片类药物2.5次。在四种实验条件中的每一种条件下，给予三次IM吗啡注射（每次18 mg/70 kg）。实验条件涉及间隔注射在12-，24-，48-或72-h的间隔。在最后一次吗啡暴露后24小时给予纳洛酮（10 mg/70 kg IM）。包括比较条件，其中在单次IM吗啡预处理（18 mg/70 kg）后24 h给予纳洛酮激发。受试者评定的症状和体征的测量结果表明，戒断强度与吗啡间隔时间呈负相关，特别是在间隔12小时的三次预处理后沉淀的戒断强度大于单次吗啡预处理后沉淀的强度。生理数据支持在12小时间隔条件下更强烈的退缩反应，并提供了血压和皮肤温度测量过冲的证据。这些研究结果与急性和慢性身体依赖之间的过渡有关;它们表明，存在一个时间窗口，在此期间，重复给予阿片类药物会导致身体依赖性的升级，但在广泛间隔的多次暴露后的依赖水平可能不大于单次暴露后的依赖水平。
We examined the effect of morphine pretreatment spacing on intensity of subsequent precipitated withdrawal response to test the hypothesis that withdrawal intensity would be inversely related to pretreatment spacing. Subjects were ten nondependent male volunteers who reported using opioids an average of 2.5 times per week. Three IM morphine injections (each 18 mg/70 kg) were administered during each of four experimental conditions. The experimental conditions involved spacing injections at 12-, 24-, 48- or 72-h intervals. Naloxone (10 mg/70 kg IM) was administered 24 h after the last morphine exposure. A comparison condition was included in which a naloxone challenge was given at 24 h following a single IM morphine pretreatment (18 mg/70 kg). Subject rated measures of symptoms and observer-rated measures of signs indicated that withdrawal intensity was inversely related to the morphine spacing interval and in particular that intensity of withdrawal precipitated after three pretreatments spaced at 12-h intervals was greater than that precipitated after a single morphine pretreatment. Physiological data supported a more intense withdrawal response in the 12-h spacing condition and provided evidence of overshoot on blood pressure and skin temperature measures. These findings are pertinent to the transition between acute and chronic physical dependence; they suggest that there is a temporal window during which repeated opioid administrations result in escalation of physical dependence but that dependence levels after widely spaced multiple exposures may be no greater than after a single exposure.