Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus:: Implications for the neurobiology of depression
Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus:: Implications for the neurobiology of depression
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DOI：
10.1016/s0006-3223(97)00484-8
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发表时间：
1998-04-15
影响因子：
10.6
通讯作者：
Watson, SJ
中科院分区：
文献类型：
--
作者：
López, JF;Chalmers, DT;Watson, SJ
背景：边缘-下丘脑-垂体-肾上腺轴和5-羟色胺系统的紊乱在抑郁症中很常见。研究压力对这两个神经生物学系统的影响可能会给我们情感疾病的病理生理学提供重要线索，并帮助我们了解压力和情绪障碍是如何相关的。我们研究了慢性不可预测的应激和抗抑郁治疗对大鼠海马5-羟色胺1A（5-HT 1A）、糖皮质激素（GR）和盐皮质激素（MR）受体水平的影响，使用原位杂交和受体放射自显影。我们还使用原位杂交来定量一小组有抑郁症史的自杀者与匹配对照组（n = 6）相比的海马5-HT 1A、GR和MR信使（mRNA）水平。我们发现，与非应激大鼠相比，慢性不可预测应激大鼠的基础血浆皮质酮显著升高，慢性应激也引起海马5-HT 1A mRNA和结合的减少。此外，慢性应激在同一区域产生MR/GR mRNA比率的改变。在接受丙咪嗪或地昔帕明抗抑郁药治疗的动物中，5-HT 1A mRNA和结合的减少以及MR/GR改变被阻止，齐美利定不能逆转应激诱导的皮质酮增加，并且在阻止海马中应激诱导的受体变化方面仅部分成功。有抑郁症史的自杀受害者表现出非常相似的变化，发现在慢性stress.Conclusions的变化：海马5-HT 1A水平和MR/GR平衡的改变可能是应激可能触发和/或维持抑郁发作的机制之一。(C)1998年生物精神病学学会。
Background: Disturbances of the limbic-hypothalamic-pituitary-adrenal axis and the serotonin system are commonly found in depressive illness. Studying the effect of stress on these two neurobiological systems may give us important clues into the pathophysiology of affective illness and help us understand how stress and mood disorders are related.Methods: We studied the effect of chronic unpredictable stress and antidepressant treatment on serotonin 1A (5-HT1A), glucocorticoid (GR), and mineralocorticoid (MR) receptor levels in rat hippocampus, using in situ hybridization and receptor autoradiography. We also used in situ hybridization to quantify hippocampal 5-HT1A, GR, and MR messenger (mRNA) levels in a small group of suicide victims with a history of depression, compared to matched controls (n = 6).Results: We found that rats subjected to chronic unpredictable stress showed a significant elevation of basal plasma corticosterone compared to nonstressed rats, Chronic stress also caused a decrease in 5-HT1A mRNA and binding in the hippocampus. In addition, chronic stress produced alterations on the MR/GR mRNA ratio in this same region. The decreases in 5-HT1A mRNA and binding, as well as the MR/GR alterations, were prevented in animals that received imipramine or desipramine antidepressant treatment, Zimelidine was unable to reverse stress-induced increases in corticosterone, and was only partially successful in preventing the stress-induced receptor changes in the hippocampus. Suicide victims with a history of depression showed changes that were very similar to the changes found in chronic stress.Conclusions: Alterations in hippocampal 5-HT1A levels and in the MR/GR balance may be one of the mechanisms by which stress may trigger and/or maintain depressive episodes. (C) 1998 Society of Biological Psychiatry.