Mood disorders: Regulation by metabotropic glutamate receptors
Open accessAbstract
Medicinal therapies for mood disorders neither fully serve the efficacy needs of patients nor are they free of side-effect issues. Although monoamine-based therapies are the primary current treatment approaches, both preclinical and clinical findings have implicated the excitatory neurotransmitter glutamate in the pathogenesis of major depressive disorders. The present commentary focuses on the metabotropic glutamate receptors and their relationship to mood disorders. Metabotropic glutamate (mGlu) receptors regulate glutamate transmission by altering the release of neurotransmitter and/or modulating the post-synaptic responses to glutamate. Convergent biochemical, pharmacological, behavioral, and clinical data will be reviewed that establish glutamatergic neurotransmission via mGlu receptors as a biologically relevant process in the regulation of mood and that these receptors may serve as novel targets for the discovery of small molecule modulators with unique antidepressant properties. Specifically, compounds that antagonize mGlu2, mGlu3, and/or mGlu5 receptors (e.g. LY341495, MGS0039, MPEP, MTEP) exhibit biochemical effects indicative of antidepressant effects as well as in vivo activity in animal models predictive of antidepressant efficacy. Both preclinical and clinical data have previously been presented to define NMDA and AMPA receptors as important targets for the modulation of major depression. In the present review, we present a model suggesting how the interplay of…
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Activation of mGluR2s can inhibit GABA release through a presynaptic mechanism.
“It was shown that activation of mGluR2s can also regulate release of other neurotransmitters: it can inhibit GABA release via a presynaptic mechanism (Bradley et al. 2000; Pilc et al. 2008).”
From Short- and Long-Term Consequences of Nicotine Exposure during Adolescence for Prefrontal Cortex Neuronal Network Function (2012) · cites this paper as Pilc et al. 2008
Prefrontal mGluR2 signaling is linked to brain disorders such as depression and schizophrenia.
“the important role of prefrontal mGluR2 signaling in cognition is stressed by its link to brain disorders such as depression and schizophrenia.”
From Short- and Long-Term Consequences of Nicotine Exposure during Adolescence for Prefrontal Cortex Neuronal Network Function (2012) · cites this paper as Pilc et al. 2008
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BackgroundMetabotropic Glutamate Receptors in the Control of Mood Disorders
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- Authors
- Pilc, A., Chaki, S., Nowak, G., & Witkin, J. M.
- Affiliations
- Jagiellonian University (PL)
- Taisho Pharmaceutical (Japan) (JP)
- Eli Lilly (United States) (US)
- Corresponding author
- Witkin, Jeffrey M.
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 75
- Issue
- 5
- Pages
- 997-1006
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W2012199810
- Cited by
- 163
- References
- 101
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 12 · 2014: 9 · 2013: 10 · 2012: 20
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- ruj.uj.edu.pl
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- metabotropic glutamate receptors, mood disorders, major depressive disorder, glutamatergic neurotransmission, antidepressant targets, mGlu5 receptor antagonists, NMDA receptor, AMPA receptors, LY341495, MPEP, MTEP
- MeSH terms
- Animals, Humans, Receptors, Metabotropic Glutamate, Mood Disorders
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 ›
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