Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance
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Psychosocial stress is associated with altered immunity, anxiety and depression. Previously we showed that repeated social defeat (RSD) promoted microglia activation and social avoidance behavior that persisted for 24days after cessation of RSD. The aim of the present study was to determine if imipramine (a tricyclic antidepressant) would reverse RSD-inducedsocial avoidance and ameliorate neuroinflammatory responses. To test this, C57BL/6 mice were divided into treatment groups. One group from RSD and controls received daily injections of imipramine for 24days, following 6 cycles of RSD. Two other groups were treated with saline. RSD mice spent significantly less time in the interaction zone when an aggressor was present in the cage. Administration of imipramine reversed social avoidance behavior, significantly increasing the interaction time, so that it was similar to that of control mice. Moreover, 24days of imipramine treatment in RSD mice significantly decreased stress-induced mRNA levels for IL-6 in brain microglia. Following ex vivo LPS stimulation, microglia from mice exposed to RSD, had higher mRNA expression of IL-6, TNF-α, and IL-1β, and this was reversed by imipramine treatment. In a second experiment, imipramine was added to drinking water confirming the reversal of social avoidant behavior and decrease in mRNA expression of IL-6 in microglia. These data suggest that the antidepressant imipramine may exert its effect, in part, by down-regulating microglial activation.
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The elevated expression of pro-inflammatory cytokines in microglia was found to be maintained for at least 24 days after the cessation of stress.
“Moreover, the elevated expression of pro-inflammatory cytokines in microglia was found to be maintained for at least 24 days after the cessation of stress (Ramirez et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Ramirez et al, 2015
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- Authors
- Ramirez, K., Shea, D. T., McKim, D. B., Reader, B. F., & Sheridan, J. F.
- Affiliations
- The Ohio State University Wexner Medical Center (US)
- Corresponding author
- Sheridan, John F.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 46
- Pages
- 212-220
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4414808
- OpenAlex
- W1972330598
- Cited by
- 108
- References
- 51
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11 · 2023: 3 · 2022: 12 · 2021: 17 · 2020: 11 · 2019: 13 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 3
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (publishedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH097243, R01MH093473)
- National Institute of Dental and Craniofacial Research (T32DE014320)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- imipramine, repeated social defeat, social avoidance, microglial activation, neuroinflammation, psychosocial stress, interleukin-6, TNF-α, IL-1β, tricyclic antidepressants, depression, anxiety, lipopolysaccharide stimulation, brain microglia
- MeSH terms
- Animals, Antidepressive Agents, Tricyclic, Behavior, Animal, Brain, Imipramine, Lipopolysaccharides, Male, Mice, Inbred C57BL, Social Behavior, Stress, Psychological, Tumor Necrosis Factor-alpha, Interleukin-6, Microglia, Mice, Interleukin-1beta
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