Opposing roles of mGluR8 in measures of anxiety involving non-social and social challenges
Open accessAbstract
Metabotropic glutamate receptors (mGluRs) modulate glutamatergic and GABAergic neurotransmission. mGluR8, a member of group III receptors, is generally located presynaptically where it regulates neurotransmitter release. Previously we reported higher measures of anxiety in 6- and 12-month-old mGluR8(-/-) male mice than age- and sex-matched wild-type mice and that acute pharmacological stimulation with the mGluR8 agonist (S)-3,4,-dicarboxyphenylglycine (DCPG) or the Positive Allosteric Modulator (PAM) AZ12216052 reduced measures of anxiety in wild-type mice. As in humans and animals, ageing is associated with enhanced measures of anxiety following non-social and social challenges, increased understanding of these measures and how to potentially modulate them is particularly important in the elderly. Here we determined whether the effects of AZ12216052 on measures of anxiety are mediated by mGluR8 using 24-month-old mGluR8(-/-) and wild-type male mice. AZ12216052 also reduced measures of anxiety in the elevated zero maze and the acoustic startle response in mGluR8(-/-) mice. The remaining anxiolytic effects of AZ12216052 in mGluR8(-/-) mice might involve mGluR4, as the mGluR4 PAM VU 0155041 also reduced measures of anxiety in wild-type mice. In contrast, mGluR8(-/-) mice show enhanced social interaction but AZ12216052 does not affect social interaction in wild-type mice. Thus, while mGluR8 is an attractive target to modulate measures of anxiety and social interaction, the effects of AZ12216052 on measures of anxiety likely also involve receptors other than mGluR8.
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Ablation of GRM7 can make mice less fearful and less aggressive.
“In another contrast with GRM2 and the Group II subfamily as a whole, ablation of GRM7 can make mice less fearful and less aggressive (Duvoisin et al., 2011;Masugi et al., 1999;Masugi-Tokita et al., 2016) correlating with a severe reduction in neuronal activity in the BNST.”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Duvoisin et al., 2011
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References 33 · Cited by 40
- Authors
- Duvoisin, R. M., Villasana, L., Davis, M. J., Winder, D. G., & Raber, J.
- Affiliations
- Oregon Health & Science University (US)
- Vanderbilt University (US)
- Oregon National Primate Research Center (US)
- Corresponding author
- Raber, Jacob
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 221
- Issue
- 1
- Pages
- 50-54
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC3079808
- OpenAlex
- W2075430762
- Cited by
- 40
- References
- 33
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 10 · 2013: 6 · 2012: 7
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- AstraZeneca
- National Institute of Mental Health (R01 MH77647, R01MH077647)
- 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 › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- mGluR8, metabotropic glutamate receptors, group III mGluRs, anxiety, positive allosteric modulators, mGluR4, aging, social interaction, acoustic startle response, elevated zero maze, anxiolytic effects
- MeSH terms
- Acetanilides, Aging, Anilides, Animals, Anxiety, Cyclohexanecarboxylic Acids, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Interpersonal Relations, Male, Mice, Inbred C57BL, Thioglycolates, Receptors, Metabotropic Glutamate, Mice, Knockout, Maze Learning, Mice, Sensory Gating
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