Cited by 71Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Stimulation of P2Y1 receptors causes anxiolytic-like effects in the rat elevated plus-maze: Implications for the involvement of P2Y1 receptor-mediated nitric oxide production

Kittner, Holger, Franke, Heike, Fischer, Wolfgang, Schultheis, Nina, Krügel, Ute, Illes, Peter·2003·Neuropsychopharmacology

Abstract

The widespread and abundant distribution of P2Y receptors in the mammalian brain suggests important functions for these receptors in the CNS. To study a possible involvement of the P2Y receptors in the regulation of fear and anxiety, the influences of the P2Y(1,11,12) receptor-specific agonist adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS), the P2X(1,3) receptor agonist alpha,beta-methylene ATP (alpha,betameATP), the unspecific P2 receptor antagonist pyridoxalphosphate-6-azopheny l-2',4'-disulfonic acid (PPADS), and the specific P2Y(1) receptor antagonist N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS 2179) on the elevated plus-maze behavior of the rat were investigated. All tested compounds were given intracerebroventricularly (0.5 microl). ADPbetaS (50 and 500 fmol) produced an anxiolytic-like behavioral profile reflected by an increase of the open arm exploration. The anxiolytic-like effects were antagonized by pretreatment with PPADS (5 pmol) or MRS 2179 (5 pmol). Both compounds caused anxiogenic-like effects when given alone. Furthermore, the anxiolytic-like effects of ADPbetaS could be antagonized by pretreatment with the nitric oxide synthase (NOS) inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME). In addition, the anxiogenic-like effects of PPADS were reversed by the pretreatment with L-arginine (500 pmol), which is the natural substrate for NOS, but not by D-arginine (500 pmol), which is not. Immunofluorescence staining revealed the presence of P2Y(1) receptors on neurons in different brain regions such as hypothalamus, amygdala, hippocampus and the periaqueductal gray. Furthermore, the colocalization of P2Y(1) receptors and neuronal NOS (nNOS) on some neurons in these regions could be demonstrated. The highest density of P2Y(1)- and nNOS-immunoreactivity was detected in the dorsomedial hypothalamic nucleus. Taken together, the present results suggest that P2Y(1) receptors are involved in the modulation of anxiety in the rat. The anxiolytic-like effects after stimulation of P2Y(1) receptors seem to be in close connection with the related nitric oxide production.

Integrity signals

Registry

Crossref · 10.1038/sj.npp.1300043

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 [128]

  • P2R are co-localized with nNOS in some brain regions, including the hippocampus.

    “Indeed, a double immunofluorescence study have shown that P2R are co-localized with nNOS in some brain regions, including the hippocampus [128].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [128]

  • 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 [128]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Kittner, H., Franke, H., Fischer, W., Schultheis, N., Krügel, U., & Illes, P.
Affiliations
Leipzig University (DE)
Corresponding author
Kittner, Holger
Venue
Neuropsychopharmacology
Published
2002-07-25
Volume
28
Issue
3
Pages
435-444
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W2041163057
Cited by
71
References
68
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 2
FWCI
2.58
Type
journal article
Language
en
Open access
closed
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
P2Y1 receptor, purinergic receptors, anxiolytic-like behavior, anxiety, nitric oxide, neuronal nitric oxide synthase, ADPbetaS, MRS2179, PPADS, alpha,beta-methylene ATP, L-NAME, L-arginine, dorsomedial hypothalamus, amygdala, hippocampus, periaqueductal gray
MeSH terms
Animals, Anxiety, Dorsomedial Hypothalamic Nucleus, Enzyme Inhibitors, Male, Nitric Oxide, Rats, Wistar, Receptors, Purinergic P2, Maze Learning, Nitric Oxide Synthase, Rats, Nitric Oxide Synthase Type I, Receptors, Purinergic P2Y1, Purinergic P2 Receptor Agonists

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review