Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice
Open accessAbstract
Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2-/- knockout (KO) mice to explore the physiological role of mGluR2 in brain function. Although, under general observation, mGluR2-/- KO mice appeared to have no behavioral abnormalities, they exhibited several lines of behavioral alterations in the enforcing and defined behavioral tests. They showed a significant increase in locomotor sensitization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine. Upon in vivo microdialysis analysis after cocaine administration, not only did extracellular levels of dopamine increase but also the response pattern of glutamate release markedly changed in the nucleus accumbens of mGluR2-/- KO mice. The mGluR2-/- KO mice also showed significant impairment in motor coordination in the accelerating rota-rod test and exhibited hyperlocomotion in novel environmental and stressful conditions, when assessed by the open-field and forced-swim tests. These results indicate that the inhibitory mGluR2 plays a pivotal role in synaptic regulation of glutamatergic transmission in the neural network.
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Knockout of GRM2 correlates with increased stress in social interactions.
“Knockout of GRM2 has been shown to correlate with increased stress in social interactions (Morishima et al., 2005).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Morishima et al., 2005
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- Authors
- Morishima, Y., Miyakawa, T., Furuyashiki, T., Tanaka, Y., Mizuma, H., & Nakanishi, S.
- Affiliations
- Kyoto University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-03-07
- Volume
- 102
- Issue
- 11
- Pages
- 4170-4175
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC554835
- OpenAlex
- W2059164249
- Cited by
- 148
- References
- 59
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 10 · 2012: 6
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- mGluR2, cocaine, cocaine dependence, locomotor sensitization, conditioned place preference, dopamine release, nucleus accumbens, glutamate release, motor coordination, hyperlocomotion, stress response, glutamatergic neurotransmission
- MeSH terms
- Animals, Cocaine, Dopamine, Locomotion, Motor Skills, Nucleus Accumbens, Time Factors, Behavior, Addictive, Receptors, Metabotropic Glutamate, Mice, Knockout, Glutamic Acid, Mice
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