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目的：探讨二氢埃托啡（ＤＨＥ）耐受的机制．方法：放免法及反相高效液相色谱荧光检测法测定环腺苷一磷酸（ｃＡＭＰ）及谷氨酸（Ｇｌｕ）、门冬氨酸（Ａｓｐ）、谷氨酰氨（Ｇｌｎ）、ＧＡＢＡ的含量．结果：ＤＨＥ反复ｓｃ８ｄ后产生耐受．小鼠去小脑全脑Ｇｌｕ、Ａｓｐ、ＧＡＢＡ的基础含量分别由对照组的１４１±２１、３０±０４、１８±０８升高至耐受组的１７２±２２、４１±０６、３２±１０μｍｏｌ／ｇ组织，Ｇｌｎ的含量无明显改变．下丘脑及纹状体的ｃＡＭＰ基础含量分别由对照组的２７１±３８、１８９±３１降至耐受组的９６±１５、６５±２１ｎｍｏｌ／ｇ组织，大脑皮层ｃＡＭＰ的含量无明显改变．结论：ＤＨＥ耐受与脑内Ｇｌｕ、Ａｓｐ、ＧＡＢＡ基础含量的升高及下丘脑、纹状体内ｃＡＭＰ的基础含量的降低有关．
Objective: To investigate the mechanism of dihydroetorphine (DHE) tolerance. Methods: The contents of cAMP, Asp, Gln and GABA were determined by radioimmunoassay and reverse-phase high performance liquid chromatography (HPLC) . Results: DHE developed resistance after repeated sc8d. The basal levels of Glu, Asp and GABA in the cerebellum were increased from 141 ± 21,30 ± 04,18 ± 08 in the control group to 17 2 ± 22, 41 ± 06, 3 2 ± 1 0μmol / g tissue, Gln content did not change significantly. The content of cAMP in the hypothalamus and striatum decreased from 271 ± 38,189 ± 31 in the control group to 96 ± 15,65 ± 21 nmol / g in the tolerated group, respectively. There was no significant change in cAMP content in the cerebral cortex. CONCLUSION: DHE tolerance is related to the increase of basal levels of Glu, Asp and GABA, and the decrease of basal cAMP content in hypothalamus and striatum.