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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >mu-Opioid receptor downregulation contributes to opioid tolerance in vivo.
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mu-Opioid receptor downregulation contributes to opioid tolerance in vivo.

机译：mu阿片受体的下调有助于体内的阿片耐受性。

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The present study examined the contribution of downregulation of mu-opioid receptors to opioid tolerance in an intact animal model. Mice were implanted subcutaneously with osmotic minipumps that infused etorphine (50-250 microg/kg/day) for 7 days. Other mice were implanted subcutaneously with a morphine pellet (25 mg) or a morphine pellet plus an osmotic minipump that infused morphine (5-40 mg/kg/day) for 7 days. Controls were implanted with an inert placebo pellet. At the end of treatment, pumps and pellets were removed, and saturation binding studies were conducted in whole brain ([3H]DAMGO) or morphine and etorphine analgesic ED(50)s were determined (tail-flick). Morphine tolerance increased linearly with the infusion dose of morphine (ED(50) shift at highest infusion dose, 4.76). No significant downregulation of mu-receptors in whole brain was observed at the highest morphine treatment dose. Etorphine produced dose-dependent downregulation of mu-opioid receptor density and tolerance (ED(50) shift at highest infusion dose, 6.97). Downregulation of mu-receptors only occurred at the higher etorphine infusion doses (> or =150 microg/kg/day). Unlike morphine tolerance, the magnitude of etorphine tolerance was a nonlinear function of the dose and increased markedly at infusion doses that produced downregulation. These results suggest that mu-opioid receptor downregulation contributes to opioid tolerance in vivo. Therefore, opioid tolerance appears to rely upon both "receptor density-dependent" and " receptor density-independent" mechanisms.
机译：本研究检查了完整动物模型中mu阿片受体的下调对阿片耐受的影响。小鼠皮下植入渗透性微型泵，该微型泵输注了吗啡（50-250微克/千克/天），持续7天。将其他小鼠皮下植入吗啡颗粒（25 mg）或吗啡颗粒加上渗透了吗啡（5-40 mg / kg /天）的渗透性微型泵，持续7天。对照植入惰性安慰剂小丸。在治疗结束时，移除泵和小丸，并在全脑（[3H] DAMGO）或吗啡中进行饱和结合研究，并确定吗啡和依托啡定镇痛剂ED（50）（甩尾）。吗啡的耐受性随吗啡的注入剂量呈线性增加（最高注入剂量为4.76时ED（50）移动）。在最高吗啡治疗剂量下，未观察到全脑中mu受体的显着下调。埃托啡产生剂量依赖性的下阿片类阿片受体密度和耐受性下调（最高输注剂量6.97时ED（50）移动）。 mu受体的下调仅在较高的依托啡注入剂量（>或= 150 microg / kg / day）下发生。与吗啡耐受不同，吗啡耐受的幅度是剂量的非线性函数，在产生下调的输注剂量下显着增加。这些结果表明，μ阿片受体的下调有助于体内的阿片耐受性。因此，阿片样物质耐受性似乎依赖于“受体密度依赖性”和“受体密度依赖性”机制。

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