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哺乳动物冬眠者对阿片类药物体温调节反应的季节性差异。

Seasonal difference in thermoregulatory responses to opiates in a mammalian hibernator.

作者信息

Wang L C, Lee T F, Jourdan M L

出版信息

Pharmacol Biochem Behav. 1987 Mar;26(3):565-71. doi: 10.1016/0091-3057(87)90167-5.

Abstract

Accumulated evidence suggests that increased endogenous opioid activities may facilitate the onset of hibernation. The present study investigated the change in thermoregulatory responses following ICV infusion of morphine or [D-Ala2]-Met enkephalinamide (EK) in unanesthetized, unrestrained Columbian ground squirrels (Spermophilus columbianus) during its annual hibernation cycle. In the nonhibernating phase, low doses of either morphine (less than 160 micrograms) or EK (less than 400 micrograms) elicited a dose-related hyperthermia and an increase in heat production, whereas a higher dose of opiates caused hypothermia and a decrease in metabolic rate. Naloxone (5 mg/kg, SC) pretreatment reduced or reversed both the hyper- and hypothermic responses to opiates. Lower ambient temperature (5 degrees C) enhanced the hypothermic response and attenuated the hyperthermic response. In the hibernating phase, euthermic ground squirrels exhibited a reduced responsiveness to exogenous opiates: the hyperthermic response to low dose of morphine (10 micrograms) was significantly reduced and hyperthermia, rather than hypothermia was observed at the highest dose of morphine (160 micrograms). The reduced responsiveness to opiates observed during the hibernating phase seems to suggest a reduction in opiate receptor efficacy which is in agreement with the contention that an increase in endogenous opioid activities may be incumbent with the commencement of hibernation.

摘要

越来越多的证据表明,内源性阿片类物质活性增加可能会促进冬眠的开始。本研究调查了在未麻醉、不受限制的哥伦比亚地松鼠(Spermophilus columbianus)年度冬眠周期中,脑室内注射吗啡或[D-Ala2]-甲硫氨酸脑啡肽酰胺(EK)后体温调节反应的变化。在非冬眠阶段,低剂量的吗啡(小于160微克)或EK(小于400微克)会引起剂量相关的体温升高和产热增加,而高剂量的阿片类药物则会导致体温过低和代谢率降低。纳洛酮(5毫克/千克,皮下注射)预处理可降低或逆转对阿片类药物的体温过高和过低反应。较低的环境温度(5摄氏度)会增强体温过低反应并减弱体温过高反应。在冬眠阶段,正常体温的地松鼠对外源性阿片类药物的反应性降低:对低剂量吗啡(10微克)的体温过高反应显著降低,而在最高剂量吗啡(160微克)时观察到的是体温过高而非体温过低。在冬眠阶段观察到的对阿片类药物反应性降低似乎表明阿片受体效能降低,这与内源性阿片类物质活性增加可能与冬眠开始有关的观点一致。

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