Attila L M, Ahtee L
Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(3):193-200. doi: 10.1007/BF00502449.
To clarify the effects of withdrawal from chronic morphine treatment on cerebral noradrenaline (NA) turnover, we have measured the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of NA in five brain areas of male Wistar rats given morphine twice daily for 40 or 60 days. After the last morphine dose (50 or 70 mg/kg) the rats were withdrawn for 1, 2 or 4 days. In order to study the development of tolerance a challenge dose of 10 mg/kg of morphine was given to some of the rats. Withdrawal of morphine accelerated the alpha MT-induced NA depletion clearly in the hemispheres and the lower brain stem and slightly in the diencephalon. The acceleration was more pronounced in the brains of rats treated for 60 days than of those treated for 40 days. In the hemispheres the acceleration of NA depletion occurred at 1 and 2 days, in the diencephalon at 2 days, and in the lower brain stem at 2 and 4 days after morphine withdrawal. The most pronounced acceleration of NA depletion coincided with the maximum withdrawal-induced weight loss. The challenge dose of morphine clearly retarded the alpha MT-induced NA depletion in the hemispheres of control rats treated chronically with saline. This retardation was even more pronounced in rats withdrawn from chronic morphine treatment for 1 or 2 days. The challenge dose slightly accelerated the alpha MT-induced NA depletion in the lower brain stem of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
为阐明慢性吗啡治疗撤药对脑去甲肾上腺素（NA）周转率的影响，我们测量了每日两次给予吗啡40或60天的雄性Wistar大鼠五个脑区中α-甲基-p-酪氨酸（αMT）诱导的NA耗竭情况。在末次给予吗啡（50或70mg/kg）后，大鼠撤药1、2或4天。为研究耐受性的发展，给部分大鼠注射10mg/kg的吗啡激发剂量。吗啡撤药明显加速了αMT诱导的NA在大脑半球和低位脑干的耗竭，在间脑则轻微加速。60天治疗组大鼠大脑中的加速效应比40天治疗组更明显。在大脑半球，NA耗竭加速发生在撤药后1天和2天；在间脑，发生在2天；在低位脑干，发生在撤药后2天和4天。NA耗竭最明显的加速与撤药诱导的最大体重减轻同时出现。吗啡激发剂量明显延缓了长期用生理盐水处理的对照大鼠大脑半球中αMT诱导的NA耗竭。这种延缓在撤药1或2天的慢性吗啡治疗大鼠中更明显。激发剂量轻微加速了对照大鼠低位脑干中αMT诱导的NA耗竭。（摘要截短于250字）
