Brent P J, Chahl L A
Neuropharmacology Laboratory, Faculty of Medicine, University of Newcastle, N.S.W., Australia.
Neurochem Res. 1991 May;16(5):525-31. doi: 10.1007/BF00974870.
The effect of naloxone-precipitated withdrawal after acute morphine was studied on the concentrations of noradrenaline (NA), 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and on the metabolite/parent amine ratios MHPG/NA, DOPAC/DA and HVA/DA, in eight regions of the guinea-pig brain. Guinea-pigs were treated with a single dose of morphine sulphate (15 mg/kg s.c.) or saline (control) and 2h later with naloxone hydrochloride (15 mg/kg s.c.) to precipitate withdrawal. The animals were decapitated at 0.5 h or 1 h after naloxone injections and their brains analysed for monoamine concentrations by HPLC-ECD. At 0.5 h after naloxone-precipitated withdrawal NA and MHPG levels, and the MHPG/NA ratio, were increased in the hypothalamus, and the NA levels were increased in the hypothalamus, medulla/pons and cortex 1 h after naloxone. Naloxone-precipitated withdrawal also produced increased DA metabolism in the cortex, midbrain and medulla 0.5 h later, and in the cortex, hypothalamus and striatum 1 h later. Hence naloxone-precipitated withdrawal from acute morphine treatment produced a complex pattern of increased synthesis and metabolism of NA and DA which varied over time and with the brain region examined.
研究了急性给予吗啡后纳洛酮诱发的戒断反应对豚鼠脑八个区域去甲肾上腺素（NA）、4-羟基-3-甲氧基苯乙二醇（MHPG）、多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）浓度以及代谢物/母体胺比率MHPG/NA、DOPAC/DA和HVA/DA的影响。给豚鼠单次皮下注射硫酸吗啡（15 mg/kg）或生理盐水（对照），2小时后皮下注射盐酸纳洛酮（15 mg/kg）诱发戒断反应。在注射纳洛酮后0.5小时或1小时将动物断头，通过高效液相色谱-电化学检测法分析其脑内单胺浓度。在纳洛酮诱发戒断反应后0.5小时，下丘脑的NA和MHPG水平以及MHPG/NA比率升高，在纳洛酮注射后1小时，下丘脑、延髓/脑桥和皮质的NA水平升高。纳洛酮诱发的戒断反应在0.5小时后还使皮质、中脑和延髓的DA代谢增加，在1小时后使皮质、下丘脑和纹状体的DA代谢增加。因此，急性吗啡治疗后纳洛酮诱发的戒断反应产生了NA和DA合成与代谢增加的复杂模式，这种模式随时间和所检测的脑区而变化。
