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为探讨急性吗啡耐受的分子机制，本研究观察了急性吗啡耐受对大鼠脑内与奖赏系统有关核团中前脑啡肽原、前强啡肽原和κ受体基因表达的影响。２４只雄性Ｗｉｓｔａｒ大鼠连续注射６次硫酸吗啡（６．２５ｍｇ／ｋｇ）或等体积生理盐水（１ｍｌ／ｋｇ），每两次注射间期为２ｈ。在最后一次注射后３０ｍｉｎ，断头取检测样品：全脑（除去皮层，小脑和低位脑干）、伏核、尾壳核、黑质。用灵敏的液相杂交ＲＮＡ酶保护分析法检测ｍＲＮＡ水平（ｐｇｍＲＮＡ／μｇ总ＲＮＡ）。结果显示：大鼠急性吗啡耐受时中枢神经系统强啡肽和κ受体基因ｍＲＮＡ增加（即基因表达增强），但不影响脑啡肽基因表达。以上结果提示强啡肽－κ受体系统可能参与了急性吗啡耐受的形成。此外，尾壳核前强啡肽基因表达增强、黑质κ受体表达减弱，提示多次吗啡注射影响了脑内与奖赏系统有关核团中强啡肽－κ受体系统基因的表达。
In order to explore the molecular mechanism of acute morphine tolerance, the present study investigated the effects of acute morphine tolerance on the expression of preproenkephalin, preproenorphin and kappa receptor genes in the brain related to the reward system in rats. Twenty-four male Wistar rats were injected with morphine sulfate (6.25 mg / kg) or an equal volume of normal saline (1 ml / kg) six times for 2 h. 30 min after the last injection, test samples were decapitated: whole brain (cortex, cerebellum, and low brain stem), nucleus accumbens, caudate putamen, substantia nigra. Detection of mRNA levels (pgmRNA / μg total RNA) by sensitive liquid phase hybridization RNase protection assay. The results showed that the mRNA expression of dynorphin and kappa receptor in central nervous system was increased in rats with acute morphine tolerance, but the expression of enkephalin gene was not affected. These results suggest that dynorphin-kappa receptor system may be involved in the formation of acute morphine tolerance. In addition, pre-dynorphin dynorphin gene expression was enhanced and substantia nigra κ receptor expression was attenuated, suggesting that multiple morphine injections affected the expression of the dynorphin-κ receptor gene in the nucleus associated with the reward system.