Lipopolysaccharide-Induced Depressive-Like Behavior is Associated with α1-Adrenoceptor Dependent Downregulation of the Membrane GluR1 Subunit in the Mouse Medial Prefrontal Cortex and Ventral Tegmental Area
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BACKGROUND: Chronic stress-induced depressive-like behavior is relevant to inflammatory immune activation. However, the neurobiological alterations in the brain following the central inflammatory immune activation remain elusive. METHODS: Therefore, we investigated the neurobiological alterations during depressive-like behavior induced in mice by systemic administration of lipopolysaccharide (LPS; 1.2 mg/kg administered twice at a 30-min interval via intraperitoneal injection). RESULTS: At 24 h after the second administration of LPS, an increased immobility time in the tail suspension test and the forced swimming test were observed, as well as reduced sucrose preference. Protein levels of the AMPA receptor GluR1 were significantly decreased at the plasma membrane in the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA), while levels of the GluR2 were increased at the plasma membrane in the nucleus accumbens (NAc) at 24h after LPS. However, total GluR1 and GluR2 protein levels in the mPFC, VTA, and NAc were not affected by LPS. Moreover, LPS facilitated release of noradrenaline in the mPFC and VTA, but not in the NAc. Consistently, systemic administration of prazosin, an α1-adrenoceptor antagonist, blocked the LPS-induced downregulation of the membrane GluR1 subunit in both the mPFC and VTA and also blocked the upregulation of the membrane GluR2 subunit in the NAc. Intracerebroventricular administration of prazosin 30 min before LPS injection abrogated the LPS-induced depressive-like behaviors. In opposition, administration of propranolol, a β-adrenoceptor antagonist, did not affect the LPS-induced downregulation of GluR1, the upregulation of GluR2, or the depressive-like behavior. CONCLUSIONS: These results suggest that LPS-activated α1-adrenoceptor-induced downregulation of membrane GluR1 in the mPFC and VTA is associated with inflammation-induced depressive-like behavior.
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Mice that develop anhedonia after systemic lipopolysaccharide have reduced plasma membrane expression of AMPA receptor subunit GluR1.
“Mice that develop anhedonia after systemic lipopolysaccharide have reduced plasma membrane expression of AMPA receptor subunit GluR1 [60]”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [60]
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- Authors
- Sekio, M., & Seki, K.
- Affiliations
- Ohu University (JP)
- Corresponding author
- Seki, Kenjiro
- ORCID
- Seki, Kenjiro
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-12-19
- Volume
- 18
- Issue
- 1
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC4368860
- OpenAlex
- W2189097770
- Cited by
- 75
- References
- 66
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 2
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (25430070)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- lipopolysaccharide, depression-like behavior, alpha1-adrenoceptors, GluR1, GluR2, AMPA receptors, medial prefrontal cortex, ventral tegmental area, nucleus accumbens, neuroinflammation, noradrenaline release, prazosin, beta-adrenergic receptors, chronic stress, tail suspension test, forced swim test, sucrose preference
- MeSH terms
- Animals, Cell Membrane, Depression, Disease Models, Animal, Lipopolysaccharides, Male, Norepinephrine, Nucleus Accumbens, Prazosin, Down-Regulation, Prefrontal Cortex, Ventral Tegmental Area, Receptors, AMPA, Receptor, Adenosine A1, Mice, Adrenergic alpha-1 Receptor Antagonists
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