Intracerebroventricular Administration of Interferon-Alpha Induced Depressive-Like Behaviors and Neurotransmitter Changes in Rhesus Monkeys.
Intracerebroventricular Administration of Interferon-Alpha Induced Depressive-Like Behaviors and Neurotransmitter Changes in Rhesus Monkeys.
复制标题
干扰素-α的脑室内给药引起恒河猴的抑郁样行为和神经递质变化。
DOI：
10.3389/fnins.2020.585604
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发表时间：
2020
影响因子：
4.3
通讯作者：
Qin D
中科院分区：
文献类型：
--
作者：
Li Z;Li Z;Lv X;Li Z;Xiong L;Hu X;Qin D
干扰素-α是一种广泛用于治疗脑癌和病毒感染的细胞因子，其副作用包括导致抑郁症。已发现单胺类神经递质系统在外周型干扰素-α诱导的抑郁中起重要作用，但外周型干扰素-α如何进入中枢神经系统并参与抑郁症的发生发展尚不清楚。本研究旨在建立一个非人类灵长类动物模型使用长期脑室(i.c.v.)给予干扰素-α(5天/周，连续6周)，观察诱发的抑郁样行为，探讨单胺类神经递质系统在抑郁发病中的作用。在接受I.C.V.的猴子身上。给予干扰素-α后，大鼠快感减退，表现为蔗糖消耗量减少，并伴有抑郁样症状，包括抱抱行为增加，在家中笼中自发和反应性活动减少，以及在野外探索减少和静止增加。脑脊液中去甲肾上腺素(NA)、3，4-二羟基苯乙酸(DOPAC)、5-羟基吲哚乙酸(5-HIAA)和高香草酸(HVA)浓度无明显变化，但慢性中枢注射干扰素-α可显著增加脑脊液中去甲肾上腺素(NA)和3，4-二羟基苯乙酸(DOPAC)的含量。这些脑脊液单胺类代谢产物与某些特定的抑郁症相关行为有关。总之，中枢注射干扰素-α可引起快感减退和抑郁相关行为，与外周注射的结果相当，抑郁的发生与单胺类神经递质功能障碍有关。
Interferon-alpha (IFN-α) is a cytokine widely used in the treatment of brain cancers and virus infections with side effects including causing depression. Monoamine neurotransmitter systems have been found playing important roles in peripheral IFN-α-induced depression, but how peripheral IFN-α accesses the central nervous system and contributes to the development of depression is poorly known. This study aimed to develop a non-human primate model using long-term intracerebroventricular (i.c.v.) administration of IFN-α (5 days/week for 6 weeks), to observe the induced depressive-like behaviors and to explore the contributions of monoamine neurotransmitter systems in the development of depression. In monkeys receiving i.c.v. IFN-α administration, anhedonia was observed as decreases of sucrose consumption, along with depressive-like symptoms including increased huddling behavior, decreases of spontaneous and reactive locomotion in home cage, as well as reduced exploration and increased motionless in the open field. Chronic central IFN-α infusion significantly increased the cerebrospinal fluid (CSF) concentrations of noradrenaline (NA), and 3,4-dihydroxyphenylacetic acid (DOPAC), but not 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). These CSF monoamine metabolites showed associations with some specific depression-related behaviors. In conclusion, central IFN-α administration induced anhedonia and depression-related behaviors comparable to the results with peripheral administration, and the development of depression was associated with the dysfunction of monoamine neurotransmitters.
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影响因子：
7.4
作者：
Felger JC;Miller AH
通讯作者：
Miller AH
影响因子：
3.3
作者：
Felger JC;Lotrich FE
通讯作者：
Lotrich FE
影响因子：
6.1
作者：
Bodnar CN;Morganti JM;Bachstetter AD
通讯作者：
Bachstetter AD
影响因子：
--
作者：
Capuron L;Pagnoni G;Drake DF;Woolwine BJ;Spivey JR;Crowe RJ;Votaw JR;Goodman MM;Miller AH
通讯作者：
Miller AH
影响因子：
10.6
作者：
Lotrich, Francis E.;Ferrell, Robert E.;Rabinovitz, Mordechai;Pollock, Bruce G.
通讯作者：
Pollock, Bruce G.