Simpkins J W, Katovich M J, Millard W J
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Psychopharmacology (Berl). 1990;102(2):213-20. doi: 10.1007/BF02245924.
Studies were undertaken to determine the effects of acute alterations in plasma glucose levels on the tail skin temperature (TST) response of morphine-dependent rats to naloxone-precipitated withdrawal. In morphine-dependent rats, treatment with dextrose at doses of 0.5 or 2.5 g/kg did not alter the normal 6.0 +/- 0.3 degrees C TST response to naloxone. However, treatment with 5, 10 or 20 g dextrose/kg, which increased plasma glucose to 250 mg/dl or greater, blocked the TST response during morphine withdrawal. In contrast, an IV injection of 2.5 IU insulin (Na-porcine)/kg, which reduced plasma glucose for 2 h, caused a delayed TST response of 4.7 +/- 0.4 degrees C in control rats and exaggerated the TST response normally observed in morphine-dependent rats treated with naloxone. Collectively, these data indicate that acute hyperglycemia can attenuate and hypoglycemia can enhance the skin vasodilation which accompanies precipitated morphine withdrawal. In view of our observation that naloxone-precipitated morphine withdrawal caused a marked increase in blood glucose, the sympathetic activation associated with opiate withdrawal may be intended to elevate blood glucose and thereby limit the manifestation of the withdrawal response.
开展了多项研究以确定血浆葡萄糖水平的急性改变对吗啡依赖大鼠对纳洛酮诱发戒断反应的尾部皮肤温度(TST)的影响。在吗啡依赖大鼠中,以0.5或2.5 g/kg剂量的葡萄糖进行处理,并未改变对纳洛酮正常的6.0±0.3℃的TST反应。然而,以5、10或20 g葡萄糖/kg进行处理,可使血浆葡萄糖升高至250 mg/dl或更高,这会阻断吗啡戒断期间的TST反应。相反,静脉注射2.5 IU胰岛素(猪源钠)/kg,可使血浆葡萄糖在2小时内降低,这在对照大鼠中引起了4.7±0.4℃的延迟TST反应,并使在用纳洛酮处理的吗啡依赖大鼠中通常观察到的TST反应增强。总体而言,这些数据表明急性高血糖可减弱,而低血糖可增强与诱发的吗啡戒断相关的皮肤血管舒张。鉴于我们观察到纳洛酮诱发的吗啡戒断会导致血糖显著升高,与阿片类药物戒断相关的交感神经激活可能旨在升高血糖,从而限制戒断反应的表现。