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Intracerebroventricular Administration of Interferon-Alpha Induced Depressive-Like Behaviors and Neurotransmitter Changes in Rhesus Monkeys
- Source :
- Frontiers in Neuroscience, Vol 14 (2020), Frontiers in Neuroscience
- Publication Year :
- 2020
- Publisher :
- Frontiers Media S.A., 2020.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
interferon-alpha
Central nervous system
Alpha interferon
intracerebroventricular administration
Open field
neurotransmitters
lcsh:RC321-571
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cerebrospinal fluid
Internal medicine
medicine
Neurotransmitter
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Original Research
rhesus monkeys
business.industry
General Neuroscience
Homovanillic acid
Anhedonia
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Monoamine neurotransmitter
chemistry
depressive-like behaviors
medicine.symptom
business
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Language :
- English
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Frontiers in Neuroscience
- Accession number :
- edsair.doi.dedup.....7282e7d2783073f43e44e834926b961b