期刊
FRONTIERS IN NEUROSCIENCE
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2020.585604
关键词
interferon-alpha; intracerebroventricular administration; rhesus monkeys; depressive-like behaviors; neurotransmitters
资金
- Key Realm R&D Program of Guangdong Province [2019B030335001]
- National Natural Science Foundation of China [31700897, 31960178, 82074421]
- Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province [2018FB053, 2019FA007]
- China Postdoctoral Science Foundation [2018M631105]
- Yunnan Provincial Academician and Expert Workstation [202005AF150017, 2019IC051]
Interferon-alpha (IFN-alpha) 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-alpha-induced depression, but how peripheral IFN-alpha 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-alpha (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-alpha 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-alpha 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-alpha 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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