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5-HT(7) 受体作为抗抑郁样行为的介质和调制物。

The 5-HT(7) receptor as a mediator and modulator of antidepressant-like behavior.

机构信息

Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

出版信息

Behav Brain Res. 2010 May 1;209(1):99-108. doi: 10.1016/j.bbr.2010.01.022. Epub 2010 Jan 25.

DOI:10.1016/j.bbr.2010.01.022
PMID:20097233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2832919/
Abstract

The 5-HT(7) receptor has been suggested as a target for treating depression since inactivation or blockade of the receptor has an antidepressant-like behavioral effect. The present study investigated possible interactions between various classes of drugs with antidepressant properties and blockade or inactivation of the 5-HT(7) receptor. Immobility despair in the tail suspension test and the forced swim test was evaluated in mice lacking the 5-HT(7) receptor (5-HT(7)(-/-)) and in wild-type controls (5-HT(7)(+/+)) following acute drug treatments. Citalopram, a selective serotonin reuptake inhibitor and widely used antidepressant, dose-dependently reduced immobility in the tail suspension test in both 5-HT(7)(+/+) and 5-HT(7)(-/-) mice. Combining doses of citalopram and the 5-HT(7) receptor antagonist SB-269970 that by themselves did not affect behavior, reduced immobility in 5-HT(7)(+/+) mice in both the tail suspension test and the forced swim test. No effect was seen in 5-HT(7)(-/-) mice. Desipramine and reboxetine, two norepinephrine reuptake inhibitors, dose-dependently reduced immobility in the tail suspension test in 5-HT(7)(+/+) mice, but had no effect in 5-HT(7)(-/-) mice. A synergistic effect between desipramine and SB-269970 was found in both behavioral tests in 5-HT(7)(+/+) mice. Reboxetine combined with SB-269970 had effect only in the forced swim test. GBR 12909, a dopamine reuptake inhibitor, dose-dependently reduced tail suspension test immobility in both genotypes. There was no interaction between GBR 12909 and SB-269970. Aripiprazole, an antipsychotic, reduced immobility in both tests in 5-HT(7)(+/+) mice, but not in 5-HT(7)(-/-) mice. The results show that the 5-HT(7) receptor is required for the observed interaction between this receptor and antidepressants such as citalopram. The data furthermore support the hypothesis that the 5-HT(7) receptor might be a suitable target for treating depression.

摘要

5-HT(7) 受体被认为是治疗抑郁症的靶点，因为该受体的失活或阻断具有抗抑郁样行为效应。本研究调查了具有抗抑郁特性的各种类药物与 5-HT(7) 受体的阻断或失活之间的可能相互作用。在缺乏 5-HT(7) 受体（5-HT(7)(-/-)）的小鼠和野生型对照（5-HT(7)(+/+)）中，评估了急性药物治疗后，5-HT(7) 受体拮抗剂 SB-269970 和选择性 5-羟色胺再摄取抑制剂西酞普兰对尾部悬挂试验和强迫游泳试验中的不动性绝望的影响。西酞普兰，一种选择性 5-羟色胺再摄取抑制剂，广泛用于治疗抑郁症，剂量依赖性地减少了尾部悬挂试验中 5-HT(7)(+/+)和 5-HT(7)(-/-)小鼠的不动性。西酞普兰和 5-HT(7) 受体拮抗剂 SB-269970 的组合剂量本身不影响行为，减少了尾部悬挂试验中 5-HT(7)(+/+)小鼠的不动性，以及强迫游泳试验。在 5-HT(7)(-/-)小鼠中未见效果。去甲肾上腺素再摄取抑制剂去甲丙咪嗪和瑞波西汀剂量依赖性地减少了尾部悬挂试验中 5-HT(7)(+/+)小鼠的不动性，但在 5-HT(7)(-/-)小鼠中没有作用。去甲丙咪嗪和 SB-269970 之间存在协同作用，在两种行为测试中均在 5-HT(7)(+/+)小鼠中发现。瑞波西汀与 SB-269970 联合仅在强迫游泳试验中有效。多巴胺再摄取抑制剂 GBR 12909 剂量依赖性地减少了两种基因型的尾部悬挂试验不动性。GBR 12909 和 SB-269970 之间没有相互作用。抗精神病药阿立哌唑减少了两种测试中 5-HT(7)(+/+)小鼠的不动性，但在 5-HT(7)(-/-)小鼠中没有。结果表明，5-HT(7) 受体是观察到的这种受体与西酞普兰等抗抑郁药之间相互作用所必需的。该数据进一步支持了 5-HT(7) 受体可能是治疗抑郁症的合适靶点的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/e49d80cac8b8/nihms176620f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/dcffe5dfd9c7/nihms176620f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/765bf4103385/nihms176620f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/604d5b322c53/nihms176620f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/8918f793915e/nihms176620f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/f6d73c28f002/nihms176620f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/e49d80cac8b8/nihms176620f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/dcffe5dfd9c7/nihms176620f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/765bf4103385/nihms176620f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/604d5b322c53/nihms176620f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/8918f793915e/nihms176620f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/f6d73c28f002/nihms176620f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/2832919/e49d80cac8b8/nihms176620f6.jpg

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