Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: Relevance for neuropsychiatric disorders
Abstract
The purinergic P2X(7) receptor is a ligand-gated ion channel found on peripheral macrophages and microglia in the nervous system. Activation of P2X(7) receptors results in the rapid release of interleukin-1 beta (IL-1 beta). Cytokines like IL-1 beta are suggested to be involved in the pathophysiology of depression. The aim of this study was to behaviorally profile P2X(7) receptor knockout (KO) mice in behavioral models of depression- and anxiety-like behaviors. P2X(7) receptor KO and wild type (WT) mice were tested in multiple models including; forced swim test, tail suspension test, elevated plus maze, novelty suppressed feeding, spontaneous locomotor activity, and food intake. P2X(7) receptor KO mice exhibited an antidepressant-like profile in tail suspension test and forced swim test; an effect that was not associated with changes in spontaneous locomotor activity. In addition, P2X(7) receptor KO mice showed higher responsivity to a subefficacious dose of the antidepressant drug imipramine (15 mg/kg) in forced swim test. No significant differences between genotypes were observed in models of anxiety. These data support the relevance of pro-inflammatory cytokines in depressive-like states, and suggest that P2X(7) receptor antagonists could be of potential interest for the treatment of affective disorders.
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P2X7R knockout mice present increased active behaviors in the forced swim test and tail suspension test.
“These mice present increased active behaviors in these tests, without changes in spontaneous locomotor activity, which can be interpreted as less depressive-like phenotype, suggesting an antidepressant-like effect of the genetic manipulation [84].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [84]
P2X7R knockout mice showed improved response to a sub-effective dose of imipramine in the forced swim test.
“Further supporting this suggestion was found in a study with P2X7R KO mice, which showed improved response to a sub-effective dose of the antidepressant drug imipramine in the FST [84].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [84]
P2X7R knockout mice show no changes in spontaneous locomotor activity.
“These mice present increased active behaviors in these tests, without changes in spontaneous locomotor activity, which can be interpreted as less depressive-like phenotype, suggesting an antidepressant-like effect of the genetic manipulation [84].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [84]
Both pharmacological and genetic evidence strongly suggest that P2X7R stimulation during stress increases vulnerability and subsequent development of behavioral adversities associated with the neurobiology of depression.
“Altogether, both pharmacological and genetic evidence strongly suggest that P2X7R stimulation during stress increase the vulnerability and subsequent development of behavioral adversities associated with the neurobiology of depression (Table 2).”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [84]
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Paroxetine suppresses recombinant human P2X7 responses
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- Authors
- Basso, A. M., Bratcher, N. A., Harris, R. R., Jarvis, M. F., Decker, M. W., & Rueter, L. E.
- Affiliations
- Abbott (United States) (US)
- Corresponding author
- Basso, Ana M.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 198
- Issue
- 1
- Pages
- 83-90
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2051314027
- Cited by
- 224
- References
- 69
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 11 · 2023: 5 · 2022: 18 · 2021: 15 · 2020: 8 · 2019: 20 · 2018: 22 · 2017: 22 · 2016: 15 · 2015: 15 · 2014: 13 · 2013: 8 · 2012: 12
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- P2X7 receptor, purinergic signaling, IL-1β, depression, anxiety, antidepressant-like behavior, microglia, macrophages, inflammatory cytokines, neuropsychiatric disorders, knockout mice, locomotor activity
- MeSH terms
- Analysis of Variance, Animals, Antidepressive Agents, Tricyclic, Anxiety, Behavior, Animal, Depression, Disease Models, Animal, Eating, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Imipramine, Male, Mice, Inbred C57BL, Motor Activity, Swimming, Polymerase Chain Reaction, Receptors, Purinergic P2, Mice, Knockout, Maze Learning, Hindlimb Suspension, Mice, Interleukin-1beta
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