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Cited by 109Adenosine and Purinergic SignalingStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test

Boucher, A.A., Arnold, J.C., Hunt, G.E., Spiro, A., Spencer, J., Brown, C., McGregor, I.S., Bennett, M.R. +1 more·2011·Neuroscience
DOI 10.1016/j.neuroscience.2011.05.049
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Abstract

There is considerable evidence suggesting genetic factors play an important role in the pathophysiology of depression, possibly by increasing susceptibility to repeated environmental stressors. Recent linkage studies have associated a polymorphism of the gene coding for the P2X7 receptor (P2X7R) with both major depressive disorder and bipolar disorder. Here we assessed whether P2X7 deletion affected the behavioural and neural response to repeated stress. P2X7R knockout (P2X7-/-) mice were subjected to the forced swim test for three consecutive days and neuronal activation in response to the third exposure was assessed using c-Fos immunohistochemistry. In addition, anxiety was evaluated in another group of P2X7-/- mice using the elevated plus maze (EPM) and light dark emergence (LDE) tests. Equivalent levels of immobility were observed in P2X7-/- mice and wild-type (WT) mice on the first exposure to forced swim, but much greater immobility was seen in WT mice on second and third exposures. This suggests that P2X7-/- mice exhibit an impaired adaptive coping response to repeated stress. Reinforcing this view, c-Fos expression in the dentate gyrus of the hippocampus and in the basolateral amygdala was seen in WT mice but not P2X7-/- mice following repeated forced swim. In addition, decreased locomotor activity was detected in P2X7-/- mice without any specific effects on anxiety in the LDE test. However, P2X7-/- mice showed greater anxiety-like behaviour in the EPM. These data suggest that the P2X7R may be involved in the adaptive mechanisms elicited by exposure to repeated environmental stressors that leads to the development of depression-like behaviours. This suggests that P2X7R antagonists may be useful therapeutics for the treatment of major depression, possibly by increasing resilience in the face of repeated stress.

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  • The changed behavioral phenotype of P2X7R knockout mice was only observed when mice were repeatedly exposed to the forced swim test.

    “In another study, however, the changed behavioral phenotype of P2X7R KO mice was only observed when mice were repeatedly exposed to the FST, indicating that absence of P2X7R-mediated signaling can facilitate behavioral adaptation upon repeated stress exposure, preventing development of depressive-like behaviors, following a single exposure to the stressful condition [86].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [86]

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Authors
Boucher, A. A., Arnold, J. C., Hunt, G. E., Spiro, A., Spencer, J., Brown, C., McGregor, I. S., Bennett, M. R., & Kassiou, M.
Affiliations
The University of Sydney (AU)
Corresponding author
Kassiou, M.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2011-08
Volume
189
Pages
170-177
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2011.05.049
OpenAlex
W1998622794
Cited by
108
References
46
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 9 · 2019: 9 · 2018: 12 · 2017: 11 · 2016: 5 · 2015: 10 · 2014: 10 · 2013: 4 · 2012: 7
FWCI
5.13
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
NHMRC
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
P2X7 receptor, P2X7 knockout mice, depression, resilience, repeated stress, forced swim test, Fos expression, dentate gyrus, basolateral amygdala, anxiety-like behavior, locomotor activity, major depressive disorder, bipolar disorder, P2X7 antagonists
MeSH terms
Animals, Anxiety, Depression, Female, Motor Activity, Stress, Psychological, Proto-Oncogene Proteins c-fos, Mice, Knockout, Maze Learning, Mice, Receptors, Purinergic P2X7

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