Differential effects of chronic antidepressant treatment on swim stress- and fluoxetine-induced secretion of corticosterone and progesterone.
Differential effects of chronic antidepressant treatment on swim stress- and fluoxetine-induced secretion of corticosterone and progesterone.
复制标题
DOI：
--
复制
发表时间：
1998-05
期刊：
影响因子：
--
通讯作者：
G. Duncan;D. Knapp;S. Carson;G. Breese
中科院分区：
文献类型：
--
作者：
G. Duncan;D. Knapp;S. Carson;G. Breese
皮质醇分泌过多发生在许多重度抑郁症患者中，并在慢性抗抑郁药治疗过程中随临床恢复而正常化。这些临床数据表明，研究抗抑郁治疗对脑-垂体-肾上腺轴调节的影响可能有助于阐明抗抑郁作用的治疗基础。在本研究中，游泳应激和急性氟西汀激发均增加皮质酮和孕酮的释放，以反映脑垂体-肾上腺轴的激活。研究了慢性抗抑郁治疗（21天）对这些挑战诱导的皮质酮和孕酮分泌的影响。长期氟西汀治疗（5 mg/kg/天）完全阻断了急性氟西汀激发后皮质酮和孕酮分泌的增加。地昔帕明、丙咪嗪或阿米替林（15 mg/kg/天）长期治疗也显著减弱氟西汀诱导的皮质酮和孕酮分泌。然而，单胺氧化酶抑制剂苯乙肼（5 mg/kg）和反苯环丙胺（5 mg/kg）的长期治疗并不影响对急性氟西汀激发的激素反应。各种慢性抗抑郁药治疗条件下，急性激发后氟西汀的血浆水平与慢性生理盐水对照组无显著差异;因此，氟西汀代谢的增加不能解释慢性抗抑郁药治疗后氟西汀诱导的激素反应的拮抗作用。与选定的抗抑郁药对急性氟西汀诱导的类固醇释放的影响相反，丙咪嗪（20 mg/kg/天）、氟西汀（5 mg/kg/天）或苯乙肼（5 mg/kg）的慢性治疗并没有显著改变这种游泳应激诱导的皮质酮或孕酮分泌。由于慢性氟西汀和三环类抗抑郁药物阻断了氟西汀增加肾上腺皮质分泌的急性作用，但没有改变游泳应激诱导的这些类固醇的分泌，我们提出不同的神经化学机制控制氟西汀和游泳应激诱导的类固醇释放。我们推测，这些慢性抗抑郁治疗，最大限度地减少急性氟西汀挑战增加皮质酮和孕酮分泌的影响，大量的适应性反应，可能与这些药物的治疗作用。
Hypersecretion of cortisol occurs in numerous patients with major depression and normalizes with clinical recovery during the course of chronic antidepressant treatment. These clinical data suggest that investigation of the effects of antidepressant treatments on the regulation of the brain-pituitary-adrenal axis may assist in elucidating the therapeutic basis of antidepressant actions. In the present investigation, both swim stress and acute fluoxetine challenge increased release of corticosterone and progesterone to reflect an activation of the brain pituitary-adrenal axis. The effects of chronic antidepressant treatment (21 days) on corticosterone and progesterone secretion induced by these challenges were investigated. Chronic fluoxetine treatment (5 mg/kg/day) completely blocked the increased secretion of corticosterone and progesterone in response to the acute fluoxetine challenge. Chronic treatment with desipramine, imipramine or amytriptyline (15 mg/kg/day) also markedly attenuated fluoxetine-induced corticosterone and progesterone secretion. However, chronic treatment with the monoamine oxidase inhibitors, phenelzine (5 mg/kg) and tranylcypromine (5 mg/kg), did not affect this hormonal response to acute fluoxetine challenge. Plasma levels of fluoxetine after acute challenge were not significantly different for the various chronic antidepressant treatment conditions from the chronic saline controls; therefore, an increase in the metabolism of fluoxetine can not explain the antagonism of the fluoxetine-induced hormonal response after chronic antidepressant treatment. In contrast to the effects of selected antidepressants on acute fluoxetine-induced steroid release, chronic treatment with imipramine (20 mg/kg/day), fluoxetine (5 mg/kg/day) or phenelzine (5 mg/kg) did not significantly alter this swim stress-induced corticosterone or progesterone secretion. Because chronic fluoxetine and tricyclic antidepressant drugs blocked the acute action of fluoxetine to increase adrenal cortical secretion, but did not alter swim stress-induced secretion of these steroids, we propose that distinct neurochemical mechanisms control fluoxetine and swim stress-induced steroid release. We speculate that the substantial adaptive response to those chronic antidepressant treatments, which minimize the effect of acute fluoxetine challenge to increase in corticosterone and progesterone secretion, may be relevant to the therapeutic actions of these drugs.