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Cited by 66Adenosine and Purinergic SignalingNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: Involvement of nitric oxide

Pereira, Vitor S., Casarotto, Plinio C., Hiroaki-Sato, Vinícius A., Sartim, Ariandra G., Guimarães, Francisco S., Joca, Sâmia R.L.·2013·European Neuropsychopharmacology
DOI 10.1016/j.euroneuro.2013.01.008
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Abstract

Activation of purinergic receptors by ATP (P2R) modulates glutamate release and the activation of post-synaptic P2R is speculated to induce nitric oxide (NO) synthesis. Increased glutamatergic and nitrergic signaling have been involved in the neurobiology of stress-related psychiatric disorders such as anxiety and depression. Therefore, the aim of this study was to test the effects of two P2R antagonists (PPADS and iso-PPADS) in animals submitted to models predictive of antidepressant-, anxiolytic- and anticompulsive-like effects. Swiss mice receiving PPADS at 12.5mg/kg showed reduced immobility time in the forced swimming test (FST) similarly to the prototype antidepressant imipramine (30mg/kg). This dose was also able to decrease the number of buried marbles in the marble-burying test (MBT), an anticompulsive-like effect. However, no effect was observed in animals submitted to the elevated plus maze (EPM) and to the open field test. The systemic administration of iso-PPADS, a preferential P2XR antagonist, also reduced the immobility time in FST, which was associated to a decrease in NOx levels in the prefrontal cortex. In addition, P2X7 receptor was found co-immunoprecipitated with neuronal nitric oxide synthase (NOS1) in the prefrontal cortex. These results suggest that P2X7, possibly coupled to NOS1, could modulate behavioral responses associated to stress-related disorders and it could be a new target for the development of more effective treatments for affective disorders.

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Crossref · 10.1016/j.euroneuro.2013.01.008

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  • Treatment with P2X7R antagonists induces antidepressant-like effects in various animal models.

    “Evidence from pharmacological studies have further corroborated this hypothesis, since treatment with P2X7R antagonists induce antidepressant-like effects in various animal models.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [87]

  • Treatment with PPADS or iso-PPADS decreased the immobility time of mice undergoing the forced swim test.

    “Similarly, our research group observed that the treatment with the non-selective P2R antagonist (pyridoxal-phosphate-6-azophenyl-2’,4’-disulfonic acid, PPADS) or with a preferential P2XR antagonist (iso-PPADS) decreased the immobility time of mice undergoing FST [87].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [87]

  • A molecular analysis suggests that P2X7R may be coupled to neuronal nitric oxide synthase in the prefrontal cortex.

    “Besides, a molecular analysis suggest that P2X7R may be coupled to neuronal nitric oxide synthase (nNOS) in prefrontal cortex [87].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [87]

  • P2X7R may modulate stress-induced consequences by facilitating NO release in limbic brain regions.

    “These results indicate that P2X7R may also modulate stress-induced consequences by facilitating NO release in limbic brain regions.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [87]

  • P2X7R stimulation may also modulate nitric oxide formation.

    “Beyond 5-HT, NA, glutamate and GABA, P2X7R stimulation may also modulate nitric oxide (NO) formation.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [87]

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Authors
Pereira, V. S., Casarotto, P. C., Hiroaki-Sato, V. A., Sartim, A. G., Guimarães, F. S., & Joca, S. R. L.
Affiliations
Universidade de São Paulo (BR)
Corresponding author
Joca, Sâmia R.L.
ORCID
Venue
European Neuropsychopharmacology
Publisher
Elsevier BV
Published
2013-12
Volume
23
Issue
12
Pages
1769-1778
ISSN
0924-977X (ISSN-L)
DOI
10.1016/j.euroneuro.2013.01.008
OpenAlex
W2081827707
Cited by
66
References
75
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 15 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 7 · 2014: 3 · 2013: 2
FWCI
4.36
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
purinergic receptors, P2X7 receptor, PPADS, nitric oxide, neuronal nitric oxide synthase, antidepressant effects, anxiolytic effects, depression, anxiety, compulsive behavior, stress-related psychiatric disorders, prefrontal cortex, glutamate release, forced swim test, marble burying test
MeSH terms
Animals, Antidepressive Agents, Brain, Compulsive Behavior, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Exploratory Behavior, Hippocampus, Male, Nitric Oxide, Pyridoxal Phosphate, Receptors, Purinergic, Swimming, Paroxetine, Maze Learning, Immobility Response, Tonic, Rats, Nitric Oxide Synthase Type II, Purinergic Antagonists

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