Flattening the corticosterone rhythm attenuates 5-HT1A autoreceptor function in the rat:: Relevance for depression
Flattening the corticosterone rhythm attenuates 5-HT1A autoreceptor function in the rat:: Relevance for depression
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DOI：
10.1038/sj.npp.1300016
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发表时间：
2003-01-01
影响因子：
7.6
通讯作者：
Gartside, SE
中科院分区：
文献类型：
--
作者：
Leitch, MM;Ingram, CD;Gartside, SE
抑郁症与糖皮质激素异常有关，特别是皮质醇昼夜节律变平。最近的数据表明，抑郁症病因学的一个重要因素可能是 5-HT1A 受体的功能和表达缺陷，这一点在抑郁症患者中已有报道。本研究评估了这种皮质醇异常是否导致 5-HT1A 受体缺陷的可能性。首先，开发了扁平糖皮质激素节律的大鼠模型。植入 14 天的控释皮质酮颗粒使皮质酮节律变平，并将水平维持在假手术大鼠观察到的最低点和最高点水平之间的恒定水平。其次，使用微透析评估海马中 5-HT 的释放，测量对 8-OHDPAT 的抑制反应以确定体细胞树突 5-HT1A 自身受体的敏感性。发现皮质酮治疗可诱导对 8-OHDPAT 的反应显着减弱，表明体细胞树突 5-HT1A 自身受体的功能脱敏。皮质酮治疗对基础细胞外 5-HT 水平没有影响。数据表明，与抑郁症相关的糖皮质激素异常可能会影响大脑中 5-HT1A 受体的功能。这些发现表明，解决皮质醇异常可能是抑郁症药物治疗的一个有价值的目标。
Depression is associated with glucocorticoid abnormalities, in particular a flattening of the diurnal cortisol rhythm. Recent data suggest that an important factor in the aetiology of depression may be a deficit in the function and expression of 5-HT1A receptors, which has been reported in depressed patients. The present study assessed the possibility that this cortisol abnormality is causal in the 5-HT1A receptor deficits. First, a rat model of flattened glucocorticoid rhythm was developed. Controlled release corticosterone pellets implanted for 14 days flattened the corticosterone rhythm and maintained levels constant midway between the nadir and zenith levels observed in sham-operated rats. Secondly, using microdialysis to assess 5-HT release in the hippocampus, the inhibitory response to 8-OHDPAT was measured to determine the sensitivity of somatodendritic 5-HT1A autoreceptors. Corticosterone treatment was found to induce a significant attenuation in the response to 8-OHDPAT, indicating functional desensitization of somatodendritic 5-HT1A autoreceptors. There was no effect of corticosterone treatment on basal extracellular 5-HT levels. The data suggest that the glucocorticoid abnormalities associated with depression may impact on the functioning of 5-HT1A receptors in the brain. These findings suggest that resolution of cortisol abnormalities may be a valuable target for pharmacotherapy in the treatment of depression.