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
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.
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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]
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P2X7 Receptor Signaling in Stress and Depression
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- 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
- Licence
- www.springer.com/tdm (tdm)
- 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
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