REPEATED MORPHINE ADMINISTRATION DOWN-REGULATES GLUCOCORTICOID, BUT NOT MINERALOCORTICOID, RECEPTORS IN THE RAT HIPPOCAMPUS
REPEATED MORPHINE ADMINISTRATION DOWN-REGULATES GLUCOCORTICOID, BUT NOT MINERALOCORTICOID, RECEPTORS IN THE RAT HIPPOCAMPUS
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DOI：
10.1016/0306-4530(94)e0043-9
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发表时间：
1995-01-01
影响因子：
3.7
通讯作者：
LASON, W
中科院分区：
文献类型：
--
作者：
BUDZISZEWSKA, B;JAWORSKA, L;LASON, W
已知下丘脑-垂体-肾上腺轴（HPA）的激活是阿片类药物神经内分泌反应的重要组成部分。由于该轴受到海马皮质类固醇受体的抑制控制，本研究旨在确定单次（20 mg/kg IP）和重复（20至100 mg/kg/天，IP，每天两次，持续10天）吗啡给药对这些受体结合参数的影响。使用选择性 GR 激动剂 RU 28362，通过体外 [H-3]-皮质酮与大鼠海马胞质中的结合来检查糖皮质激素 (GR) 和盐皮质激素 (MR) 受体，以区分 MR 和 GR。重复（而非单次）吗啡治疗可显着（降低约 22%）在 2 小时内降低 GR 密度，并在最后一次注射药物后 72 小时内趋于降低。 MR 密度在这些时间点没有变化。单次或重复给予吗啡后，未发现任何类型受体的解离常数发生变化。急性和慢性吗啡给药后1小时血浆皮质酮水平显着升高（分别为382%和527%）。这些结果表明，重复给予吗啡会下调 GR 受体，这可能会损害 HPA 活性的反馈控制机制。
Activation of the hypothalamic-pituitary-adrenal axis (HPA) is known to be an important component of a neuroendocrine response to opiates. Since this axis is under inhibitory control of hippocampal corticosteroid receptors, the present study has been designed to determine the effects of single (20 mg/kg IP) and repeated (from 20 to 100 mg/kg/day, IP, twice a day for 10 days) morphine administration on binding parameters of these receptors. Glucocorticoid (GR) and mineralocorticoid (MR) receptors were examined by an in vitro [H-3]-corticosterone binding in the cytosol from the rat hippocampus, using the selective GR agonist RU 28362 to discriminate between MR and GR. Repeated, but not single, treatment with morphine significantly (by similar to 22%) reduced the density of GR at 2 h and tended to decrease it at 72 h after the last drug injection. The density of MR was unchanged at those time points. No changes in dissociation constants of either type of the receptors were found following single or repeated morphine administration. The plasma corticosterone level was significantly increased 1 h after acute and chronic administration of morphine (382 and 527%, respectively). These results indicate that repeated morphine administration downregulates GR receptors, which may impair the feedback control mechanism of the HPA activity.