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Antidepressants of different classes cause distinct behavioral and brain pro- and anti-inflammatory changes in mice submitted to an inflammatory model of depression
- Source :
- Journal of Affective Disorders. 268:188-200
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Background Depressed patients present increased plasma levels of lipopolysaccharide (LPS) and neuroinflammatory alterations. Here, we determined the neuroimmune effects of different classes of ADs by using the LPS inflammatory model of depression. Methods Male rats received amitriptyline (AMI) a tricyclic, S-citalopram (ESC) a selective serotonin reuptake inhibitor, tranylcypromine (TCP) a monoamine oxidase inhibitor, vortioxetine (VORT) a multimodal AD or saline for ten days. One-hour after the last AD administration, rats were exposed to LPS 0.83 mg/kg or saline and 24 h later were tested for depressive-like behavior. Plasma corticosterone, brain levels of nitrite, pro- and anti-inflammatory cytokines, phospho-cAMP Response Element-Binding Protein (CREB) and nuclear factor (NF)-kB p 65 were determined. Results LPS induced despair-like, impaired motivation/self-care behavior and caused anhedonia. All ADs prevented LPS-induced despair-like behavior, but only VORT rescued impaired self-care behavior. All ADs prevented LPS-induced increase in brain pro-inflammatory cytokines [interleukin (IL)-1β and IL-6] and T-helper 1 cytokines [tumor necrosis factor (TNF)-α and interferon-γ]. VORT increased striatal and hypothalamic IL-4 levels. All ADs prevented LPS-induced neuroendocrine alterations represented by increased levels of hypothalamic nitrite and plasma corticosterone response. VORT and ESC prevented LPS-induced increase in NF-kBp65 hippocampal expression, while ESC, TCP and VORT, but not IMI, prevented the alterations in phospho-CREB expression. Limitations LPS model helps to understand depression in a subset of depressed patients with immune activation. The levels of neurotransmitters were not determined. Conclusion This study provides new evidence for the immunomodulatory effects of ADs, and shows a possible superior anti-inflammatory profile of TCP and VORT.
- Subjects :
- Lipopolysaccharides
Male
medicine.medical_specialty
Lipopolysaccharide
medicine.drug_class
Serotonin reuptake inhibitor
Interleukin-1beta
Anti-Inflammatory Agents
Citalopram
Hippocampus
Interferon-gamma
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Humans
Amitriptyline
Neuroinflammation
Monoamine oxidase inhibitor
Depression
Tumor Necrosis Factor-alpha
business.industry
Tranylcypromine
Brain
Interleukin
Antidepressive Agents
Rats
030227 psychiatry
Psychiatry and Mental health
Clinical Psychology
Endocrinology
chemistry
Cytokines
Tumor necrosis factor alpha
Corticosterone
business
Selective Serotonin Reuptake Inhibitors
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 01650327
- Volume :
- 268
- Database :
- OpenAIRE
- Journal :
- Journal of Affective Disorders
- Accession number :
- edsair.doi.dedup.....6d2137cb1afc2c2654bb504c26b4c353