Cited by 141Deep Brain Stimulation and Movement DisordersNeuroscience and Neuropharmacology ResearchParkinson's Disease Mechanisms and Treatments

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Activation of Group II Metabotropic Glutamate Receptors Inhibits Synaptic Excitation of the Substantia Nigra Pars Reticulata

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Bradley, Stefania Risso, Marino, Michael J., Wittmann, Marion, Rouse, Susan T., Awad, Hazar, Levey, Allan I., Conn, P. Jeffrey·2000·The Journal of Neuroscience

DOI 10.1523/jneurosci.20-09-03085.2000PMC PMC6773118

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Abstract

Loss of nigrostriatal dopaminergic neurons in Parkinson's disease (PD) leads to increased activity of glutamatergic neurons in the subthalamic nucleus (STN). Recent studies reveal that the resultant increase in STN-induced excitation of basal ganglia output nuclei is responsible for the disabling motor impairment characteristic of PD. On the basis of this, it is possible that any manipulation that reduces activity at excitatory STN synapses onto basal ganglia output nuclei could be useful in the treatment of PD. We now report that group II metabotropic glutamate receptors (mGluRs) are presynaptically localized on STN terminals and that activation of these receptors inhibits excitatory transmission at STN synapses. In agreement with the hypothesis that this could provide a therapeutic benefit in PD, a selective agonist of group II mGluRs induces a dramatic reversal of catalepsy in a rat model of PD. These results raise the exciting possibility that selective agonists of group II mGluRs could provide an entirely new approach to the treatment of PD. These novel therapeutic agents would provide a noninvasive pharmacological treatment that does not involve the manipulation of dopaminergic systems, thus avoiding the problems associated with current therapies.

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Authors: Bradley, S. R., Marino, M. J., Wittmann, M., Rouse, S. T., Awad, H., Levey, A. I., & Conn, P. J.
Affiliations: University of Tübingen (DE)
Emory University (US)
ORCID: Marino, Michael J.
Levey, Allan I.
Conn, P. Jeffrey
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2000-05-01
Volume: 20
Issue: 9
Pages: 3085-3094
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.20-09-03085.2000
PMC: PMC6773118
OpenAlex: W1926939570
Cited by: 141
References: 54
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 6
FWCI: 10.28
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Journal of Neuroscience Nursing
Funders: National Parkinson Foundation
Emory University
National Institutes of Health
U.S. Army
Parkinsonfonden
Topics: Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: group II metabotropic glutamate receptors, substantia nigra pars reticulata, subthalamic nucleus, Parkinson's disease, basal ganglia, glutamatergic synapses, presynaptic inhibition, catalepsy, mGluR agonists, glutamatergic neurons
MeSH terms: Animals, Bridged Bicyclo Compounds, Catalepsy, Haloperidol, Male, Parkinson Disease, Substantia Nigra, Rats, Sprague-Dawley, Receptors, Presynaptic, Receptors, Metabotropic Glutamate, Dopamine Antagonists, Excitatory Amino Acid Agonists, Glutamic Acid, Excitatory Postsynaptic Potentials, Subthalamic Nucleus, Rats

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Activation of Group II Metabotropic Glutamate Receptors Inhibits Synaptic Excitation of the Substantia Nigra Pars Reticulata

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