Rubino T, Parenti M, Patrini G, Massi P, Parolaro D
Institute of Pharmacology, Faculty of Sciences, Milan, Italy.
Eur J Neurosci. 1995 Nov 1;7(11):2334-40. doi: 10.1111/j.1460-9568.1995.tb00654.x.
We followed the changes in G protein alpha subunit expression and levels throughout the brain during the naltrexone-precipitated withdrawal syndrome in morphine-dependent rats. Intraperitoneally injected naltrexone (10 mg/kg) in rats made tolerant to morphine resulted in sustained withdrawal. Additional naltrexone doses 6, 24 and 72 h later still induced a significant abstinence syndrome. At the fifth naltrexone injection (8 days later) counted signs were completely resolved but checked ones were not. Besides the behavioural modifications, opiate withdrawal affected G protein expression in the central nervous system. In situ hybridization showed that G alpha s and G alpha o mRNA, whose levels are increased in tolerance, changed further during opiate withdrawal. Specifically, as alpha s mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subsequent doses. However, alpha a mRNA expression in the olfactory system remained elevated after repeated naltrexone injections, declining to the control value of only after the fifth dose. The amounts of G alpha s and G alpha o protein closely followed the time course of mRNA. The relationship between behavioural and biochemical parameters is discussed, together with the regional selectivity of the modifications.
我们追踪了吗啡依赖大鼠在纳曲酮诱发的戒断综合征期间，整个大脑中G蛋白α亚基表达和水平的变化。对吗啡耐受的大鼠腹腔注射纳曲酮（10mg/kg）会导致持续戒断。在6、24和72小时后额外注射纳曲酮剂量仍会诱发显著的戒断综合征。在第五次注射纳曲酮时（8天后），计数的体征完全消失，但检查的体征仍未消失。除了行为改变外，阿片类药物戒断还影响中枢神经系统中的G蛋白表达。原位杂交显示，在耐受过程中水平升高的Gαs和Gαo mRNA在阿片类药物戒断期间进一步变化。具体而言，下丘脑的αs mRNA在第一次注射纳曲酮后减少，并在随后的剂量下达到对照水平。然而，在反复注射纳曲酮后，嗅觉系统中的αa mRNA表达仍保持升高，仅在第五次注射后降至对照值。Gαs和Gαo蛋白的量与mRNA的时间进程密切相关。我们讨论了行为和生化参数之间的关系，以及这些变化的区域选择性。
