Oishi R, Nishibori M, Itoh Y, Saeki K, Fukuda T, Araki Y
Department of Pharmacology, Okayama University Medical School, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):58-63. doi: 10.1007/BF00169477.
The turnover of brain histamine was examined in mice implanted subcutaneously with a morphine pellet (50 mg free base). The numbers of naloxone-precipitated jumpings and body shakes were maximum 2 and 3 days after implantation, respectively. The brain tele-methylhistamine level significantly increased (50% to 115%) during 12 h-3 days after implantation of a morphine pellet, whereas the histamine level remained unchanged. The accumulation of tele-methylhistamine by pargyline treatment was significantly enhanced when pargyline was administered 12 h after implantation, suggesting an enhancement of histamine turnover. However, a similar degree of the tele-methylhistamine accumulation was induced by pargyline during 1-5 days after implantation, as compared with the accumulation in the control mice implanted with a placebo pellet. In mice undergoing morphine withdrawal by either the removal of morphine pellet or the treatment with naloxone 3 days after implantation, the degree of the pargyline-induced tele-methylhistamine accumulation or the (S)-alpha-fluoromethylhistidine (alpha-FMH)-induced histamine decrease was similar to that observed in the placebo pellet-control mice. The numbers of naloxone-precipitated jumpings and body shakes occurring in mice 3 days after implantation were not significantly affected by any of L-histidine, alpha-FMH or metoprine. These results suggest that turnover of histamine in the brain is enhanced by acute morphine treatment and returns to the normal rate in the stage of chronic treatment and remains unchanged during the state of withdrawal.
对皮下植入吗啡丸（50mg游离碱）的小鼠的脑组胺周转率进行了检测。纳洛酮诱发的跳跃次数和身体抖动次数分别在植入后第2天和第3天达到最大值。在植入吗啡丸后的12小时至3天内，脑tele-甲基组胺水平显著升高（50%至115%），而组胺水平保持不变。在植入后12小时给予帕吉林时，帕吉林处理导致的tele-甲基组胺积累显著增强，提示组胺周转率增强。然而，与植入安慰剂丸的对照小鼠相比，在植入后1至5天内，帕吉林诱导的tele-甲基组胺积累程度相似。在植入后3天通过取出吗啡丸或用纳洛酮处理使小鼠进行吗啡戒断时，帕吉林诱导的tele-甲基组胺积累程度或（S）-α-氟甲基组氨酸（α-FMH）诱导的组胺减少程度与安慰剂丸对照小鼠中观察到的相似。植入后3天小鼠中纳洛酮诱发的跳跃次数和身体抖动次数均未受到L-组氨酸、α-FMH或美托普利的显著影响。这些结果表明，急性吗啡处理可增强脑中组胺的周转率，在慢性处理阶段恢复至正常速率，且在戒断状态下保持不变。
