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Activation of Group II Metabotropic Glutamate Receptors Inhibits Synaptic Excitation of the Substantia Nigra Pars Reticulata
Open accessAbstract
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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“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 Bradley et al. 2000
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Metadata
- 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)
- 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
- 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
- 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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