The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y

Kask, Ants; Harro, Jaanus; von Hörsten, Stephan; Redrobe, John P.; Dumont, Yvan; Quirion, Rémi

doi:10.1016/s0149-7634(01)00066-5

Cited by 358Neuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y

Kask, Ants, Harro, Jaanus, von Hörsten, Stephan, Redrobe, John P., Dumont, Yvan, Quirion, Rémi·2002·Neuroscience & Biobehavioral Reviews

DOI 10.1016/s0149-7634(01)00066-5

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Abstract

This review aims to give a brief overview of NPY receptor distribution and physiology in the brain and summarizes series of studies, test by test and region by region, aimed at identification receptor subtypes and neuronal circuitry mediating anxiolytic-like effects of NPY. We conclude that from four known NPY receptor subtypes in the rat (Y(1), Y(2), Y(4), Y(5)), only the NPY Y(1) receptor can be linked to anxiety-regulation with certainty in the forebrain, and that NPY Y(2) receptor may have a role in the pons. Microinjection studies with NPY and NPY receptor antagonists support the hypothesis that the amygdala, the dorsal periaqueductal gray matter, dorsocaudal lateral septum and locus coeruleus form a neuroanatomical substrate that mediates anxiolytic-like effects of NPY. The release of NPY in these areas is likely phasic, as NPY receptor antagonists are silent on their own. However, constant NPY-ergic tone seems to exist in the dorsal periaqueductal gray, the only brain region where NPY Y(1) receptor antagonists had anxiogenic-like effects. We conclude that endogenous NPY has an important role in reducing anxiety and serves as a physiological stabilizer of neural activity in circuits involved in the regulation of arousal and anxiety.

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In animal studies, NPY mediates anxiolysis through mechanisms including inhibiting amygdalar activation, increasing calcineurin-induced synaptic remodelling in the basolateral amygdala via the Y1 receptor, counteracting the anxiogenic effect of CRH, reducing noradrenergic activity in the locus coeruleus, and inhibiting excitatory neurotransmission in the dorsal periaqueductal grey.
“From animal studies it is known that NPY mediates anxiolysis e.g. by inhibiting amygdalar activation and increasing calcineurin-induced synaptic remodelling in the basolateral amygdala (via the Y 1 receptor), counteracting the anxiogenic effect of CRH, reducing noradrenergic activity in the locus coeruleus and inhibiting excitatory neurotransmission in the dorsal periaqueductal grey (Kask et al.,”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Kask et al., 2002
NPY is the most abundant peptide in the brain and is expressed from the medullary brainstem to the cerebral cortex.
“NPY is the most abundant peptide in the brain and is expressed from the medullary brainstem to the cerebral cortex (for review, see [175]).”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [175]

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Authors: Kask, A., Harro, J., von Hörsten, S., Redrobe, J. P., Dumont, Y., & Quirion, R.
Affiliations: National Institute of Chemical Physics and Biophysics (EE)
University of Tartu (EE)
Douglas Mental Health University Institute (CA)
Corresponding author: Kask, Ants
ORCID: Kask, Ants
Harro, Jaanus
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2002-05
Volume: 26
Issue: 3
Pages: 259-283
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/s0149-7634(01)00066-5
OpenAlex: W1987735575
Cited by: 358
References: 311
Citations by year: 2026: 6 · 2025: 12 · 2024: 14 · 2023: 12 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 16 · 2018: 12 · 2017: 10 · 2016: 11 · 2015: 13 · 2014: 21 · 2013: 13 · 2012: 18
FWCI: 2.17
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: neuropeptide Y, NPY receptors, Y1 receptor, Y2 receptor, Y4 receptor, Y5 receptor, anxiolytic effects, anxiety regulation, neurocircuitry, amygdala, dorsal periaqueductal gray, locus coeruleus, NPY receptor antagonists, arousal
MeSH terms: Animals, Anxiety, Behavior, Animal, Brain, Brain Chemistry, Humans, Neuropeptide Y, Anti-Anxiety Agents, Receptors, Neuropeptide Y, Models, Animal

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The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y

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