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Cited by 27Adenosine and Purinergic SignalingStress Responses and CortisolNeuroinflammation and Neurodegeneration Mechanisms

The impact of the P2X7 receptor antagonist A-804598 on neuroimmune and behavioral consequences of stress

Catanzaro, Joseph M., Hueston, Cara M., Deak, Molly M., Deak, Terrence·2014·Behavioural Pharmacology
DOI 10.1097/fbp.0000000000000072
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Abstract

Stress leads to neuroinflammatory and behavioral consequences through upregulation of inflammatory-related cytokines within the central nervous system such as interleukin-1β (IL-1β), which may be indicative of microglial priming/activation. Evidence suggests that the P2X7 receptor (P2X7R) may play an important role in the synthesis and conversion of IL-1β. In a series of six experiments, adult male rats were intubated with a highly selective P2X7R antagonist (A-804598) before footshock exposure. As expected, footshock increased IL-1β and CD14 mRNA in the paraventricular nucleus, and A-804598 (25 mg/kg) partially attenuated these effects. Footshock also increased hypothalamic IL-1 protein in whole hypothalamic blocks, but no effect was observed on the formation of pro-IL-1β or IL-1β in the paraventricular nucleus as assessed using western blotting. A-804598 also did not reverse the suppression in exploration produced by stress exposure. The present findings support the use of the footshock paradigm as a method for inducing stress-related neuroimmune and behavioral changes, but the evidence to support the role of A-804598 as a potential tool to reverse such changes remains modest. This study is the first to examine the role of P2X7R in vivo following footshock exposure. Further characterization of P2X7R may have implications for understanding the relationship between stress and inflammation.

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  • Administration of A-804598 to rats through intubation failed to reverse behavioral changes caused by foot shocks.

    “However, in another study, administration of A-804598 (25 mg/kg) to rats through intubation failed to reverse behavioral changes caused by foot shocks [91].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [91]

  • The divergent results with A-804598 may be explained by the different doses and administration routes used in each study.

    “The divergent results may be explained by the different doses and administration routes of A-804598 in each study.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [91]

  • The release of IL-1β was prevented by pharmacological blockage of P2X7 with the receptor specific antagonist A-804598.

    “The release of IL-1β was prevented by pharmacological blockage of P2X 7 with the receptor specific antagonist A-804598, supporting an earlier finding that A-804598 reduces footshock-induced IL-1β gene expression (Catanzaro et al, 2014).”

    From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Catanzaro et al, 2014

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Authors
Catanzaro, J. M., Hueston, C. M., Deak, M. M., & Deak, T.
Affiliations
Binghamton University (US)
Corresponding author
Deak, Molly M.
ORCID
Hueston, Cara M.
Venue
Behavioural Pharmacology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2014-09
Volume
25
Issue
5 and 6
Pages
582-598
ISSN
0955-8810 (ISSN-L)
DOI
10.1097/fbp.0000000000000072
OpenAlex
W2398695489
Cited by
27
References
72
Citations by year
2025: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 1
FWCI
2.75
Type
journal article
Language
en
Open access
closed
Locations
  • Behavioural Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
P2X7 receptor, neuroinflammation, stress, footshock, IL-1β, CD14, paraventricular nucleus, hypothalamus, microglial activation, exploratory behavior, cytokines
MeSH terms
Animals, Electroshock, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Foot, Guanidines, Hypothalamus, Male, Psychotropic Drugs, Quinolines, RNA, Messenger, Stress, Psychological, Blotting, Western, Neuroimmunomodulation, Rats, Sprague-Dawley, Lipopolysaccharide Receptors, Rats, Interleukin-1beta, Receptors, Purinergic P2X7, Purinergic P2X Receptor Antagonists

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