Measures of anxiety, sensorimotor function, and memory in male and female mGluR4−/− mice
Open accessAbstract
Metabotropic glutamate receptors (mGluRs) are coupled to second messenger pathways via G proteins and modulate synaptic transmission. Of the eight different types of mGluRs (mGluR1-mGluR8), mGluR4, mGluR6, mGluR7, and mGluR8 are members of group III. Group III receptors are generally located presynaptically, where they regulate neurotransmitter release. Because of their role in modulating neurotransmission, mGluRs are attractive targets for therapies aimed at treating anxiety disorders. Previously we showed that the mGluR4-selective allosteric agonist VU 0155041 reduces anxiety-like behavior in wild-type male mice. Here, we explore the role of mGluR4 in adult (6-month old) and middle-aged (12-month old) male and female mice lacking this receptor. Compared to age- and sex-matched wild-type mice, middle-aged mGluR4(-/-) male mice showed increased measures of anxiety in the open field and elevated zero maze and impaired sensorimotor function on the rotarod. These changes were not seen in adult 6-month-old male mice. In contrast to the male mice, mGluR4(-/-) female mice showed reduced measures of anxiety in the open field and elevated zero maze and enhanced rotarod performance. During the hidden platform training sessions of the water maze, mGluR4(-/-) mice swam farther away from the platform than wild-type mice at 6, but not at 12, months of age. mGluR4(-/-) mice also showed enhanced amygdala-dependent cued fear conditioning. No genotype differences were seen in hippocampus-dependent contextual fear conditioning. These data indicate that effects of mGluR4 on sensorimotor function and measures of anxiety, but not cued fear conditioning, are critically modulated by sex and age.
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Activation of GRM4 reduces anxiety-like behaviors in mice, while GRM4 knockout enhances fear-conditioning responses and increases anxiety in adult but not juvenile mice.
“Activation of GRM4 (mGluR4) reduces anxiety-like behaviors in mice, while GRM4 knockout enhances fear-conditioning responses and increases anxiety in adult but not juvenile mice (Davis et al., 2012).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Davis et al., 2012
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Cites
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180 · see citing works
PHARMACOLOGY AND FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTORS
Conn, P. J., & Pin, J. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.205 · Cited by 3,083 · see citing works
The metabotropic glutamate receptors: Structure and functions
Pin, J., & Duvoisin, R. M. (1995) · Neuropharmacology · doi:10.1016/0028-3908(94)00129-g · Cited by 2,267 · see citing works
Self-citationNeurobiology of Pavlovian fear conditioning.
Maren, S. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.897 · Cited by 1,866 · see citing works
Incidence of Parkinson's Disease: Variation by Age, Gender, and Race/Ethnicity
Eeden, S. K. V. D. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg068 · Cited by 1,746 · see citing works
Neural organization of the defensive behavior system responsible for fear
Fanselow, M. S. (1994) · Psychonomic Bulletin & Review · doi:10.3758/bf03210947 · Cited by 1,000 · see citing works
Regulation of Neurotransmitter Release by Metabotropic Glutamate Receptors
Cartmell, J., & Schoepp, D. D. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750889.x · Cited by 883 · see citing works
Apolipoprotein E in animal models of CNS injury and in alzheimer's disease
Poirier, J. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90156-2 · Cited by 637 · see citing works
Metabotropic glutamate receptors as novel targets for anxiety and stress disorders
Swanson, C. J., Bures, M., Johnson, M. P., Linden, A.-M., Monn, J. A., & Schoepp, D. D. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1630 · Cited by 607 · see citing works
Dębiec, J., & Ledoux, J. E. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.018 · Cited by 602 · see citing works
The quantitative measurement of motor inco-ordination in naive mice using an accelerating rotarod
Jones, B. J., & Roberts, D. J. (1968) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1968.tb09743.x · Cited by 583 · see citing works
Brain Aging Correlates: Retardation by Hormonal-Pharmacological Treatments
Landfield, P. W., Baskin, R. K., & Pitler, T. (1981) · Science · doi:10.1126/science.6270791 · Cited by 522 · see citing works
Boulware, M. I., Weick, J. P., Becklund, B. R., Kuo, S. P., Groth, R. D., & Mermelstein, P. G. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1427-05.2005 · Cited by 379 · see citing works
Benice, T. S., Rizk, A., Kohama, S., Pfankuch, T., & Raber, J. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.08.029 · Cited by 254 · see citing works
Self-citationCorti, C., Aldegheri, L., Somogyi, P., & Ferraguti, F. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00591-7 · Cited by 243 · see citing works
Pekhletski, R., Gerlai, R. T., Overstreet, L. S., Huang, X., Agopyan, N., Slater, N. T., Abramow-Newerly, W., Roder, J., & Hampson, D. R. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-20-06364.1996 · Cited by 212 · see citing works
Maj, M. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00271-5 · Cited by 197 · see citing works
Anagnostaras, S. G. (2010) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2010.00158 · Cited by 169 · see citing works
mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity
Fendt, M., Schmid, S., Thakker, D. R., Jacobson, L. H., Yamamoto, R., Mitsukawa, K., Maier, R., Natt, F., Hüsken, D., Kelly, P. H., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002073 · Cited by 135 · see citing works
Raber, J., Akana, S. F., Bhatnagar, S., Dallman, M. F., Wong, D. T., & Mucke, L. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-05-02064.2000 · Cited by 132 · see citing works
Self-citationWeaver, A. L. (2010) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2010.00038 · Cited by 121 · see citing works
Marked regional differences of brain human apolipoprotein e expression in targeted replacement mice
Sullivan, P. M., Mace, B. E., Maeda, N., & Schmechel, D. E. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.10.011 · Cited by 113 · see citing works
Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor
Linden, A.-M., Johnson, B. G., Peters, S. C., Shannon, H. E., Tian, M., Wang, Y., Yu, J., Koster, A. M., Baez, M., & Schoepp, D. D. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00079-5 · Cited by 108 · see citing works
Duvoisin, R. M., Zhang, C., Pfankuch, T. F., O'Connor, H., Gayet‐Primo, J., Quraishi, S., & Raber, J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04210.x · Cited by 102 · cited 2× · see citing works
“Previously, higher measures of anxiety were shown in male mice lacking mGluR8 (mGluR8-/-) [5-8].”
BackgroundParkinson's prevalence estimated by a state registry
Strickland, D., & Bertoni, J. M. (2003) · Movement Disorders · doi:10.1002/mds.10619 · Cited by 102 · see citing works
Valenti, O., Mannaioni, G., Seabrook, G. R., Conn, P. J., & Marino, M. J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.080481 · Cited by 92 · see citing works
Effect of Domain Interaction on Apolipoprotein E Levels in Mouse Brain
Ramaswamy, G., Xu, Q., Huang, Y., & Weisgraber, K. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1922-05.2005 · Cited by 87 · see citing works
Apolipoprotein E isoform-dependent effects on anxiety and cognition in female TR mice
Siegel, J. A., Haley, G. E., & Raber, J. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.03.002 · Cited by 79 · see citing works
Self-citationAcute pharmacological modulation of mGluR8 reduces measures of anxiety
Duvoisin, R. M., Pfankuch, T., Wilson, J. M., Grabell, J., Chhajlani, V., Brown, D. G., Johnson, E., & Raber, J. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.04.006 · Cited by 78 · see citing works
Self-citationMglur4-Positive Allosteric Modulation as Potential Treatment for Parkinson’s Disease
Hopkins, C. R., Lindsley, C. W., & Niswender, C. M. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.38 · Cited by 67 · see citing works
Distribution of Group III mGluRs in Rat Basal Ganglia with Subtype‐Specific Antibodies
Bradley, S. R., Standaert, D. G., Levey, A. I., & Conn, P. J. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11322.x · Cited by 60 · see citing works
Distribution and functional characterization of human Nav1.3 splice variants
Thimmapaya, R., Neelands, T. R., Niforatos, W., Davis‐Taber, R., Choi, W. W., Putman, C. B., Kroeger, P. E., Packer, J. C. L., Gopalakrishnan, M., Faltynek, C. R., et al. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04155.x · Cited by 43 · see citing works
Opposing roles of mGluR8 in measures of anxiety involving non-social and social challenges
Duvoisin, R. M., Villasana, L., Davis, M. J., Winder, D. G., & Raber, J. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.02.049 · Cited by 40 · see citing works
Self-citationSex-dependent cognitive phenotype of mice lacking mGluR8
Duvoisin, R. M., Villasana, L., Pfankuch, T., & Raber, J. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.01.006 · Cited by 33 · see citing works
Self-citationMarino, M. J., Hess, J., & Liverton, N. J. (2005) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026054750263 · Cited by 32 · see citing works
Thomsen, C., & Hampson, D. R. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720835.x · Cited by 29 · see citing works
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Brites, D., & Fernandes, A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00476 · Cited by 599 · see citing works
“↓ in the MDD patient’s brain Davis et al. (2012), Lopez et al. (2014) and Rucker and McGuffin (2014) Let-7a Neuronal differentiation of embryonic neural progenitors.”
BackgroundLopez, J. P., Lim, R., Cruceanu, C., Crapper, L., Fasano, C., Labonte, B., Maussion, G., Yang, J. P., Yerko, V., Vigneault, E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3582 · Cited by 308 · see citing works
Kong, L., Chen, K., Womer, F., Jiang, W., Luo, X., Driesen, N., Liu, J., Blumberg, H., Tang, Y., Xu, K., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.02.003 · Cited by 84 · see citing works
Glutamate receptors in domestication and modern human evolution
O’Rourke, T., & Boeckx, C. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.004 · Cited by 50 · see citing works
- Authors
- Davis, M. J., Haley, T., Duvoisin, R. M., & Raber, J.
- Affiliations
- Oregon Health & Science University (US)
- Oregon National Primate Research Center (US)
- Corresponding author
- Raber, Jacob
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 229
- Issue
- 1
- Pages
- 21-28
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC3294097
- OpenAlex
- W2079387877
- Cited by
- 52
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 MH77647)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- mGluR4, anxiety-like behavior, sensorimotor function, spatial memory, sex differences, age effects, group III mGluRs, cued fear conditioning, contextual fear conditioning, rotarod performance, amygdala
- MeSH terms
- Age Factors, Analysis of Variance, Anilides, Animals, Anxiety, Body Weight, Conditioning, Psychological, Cues, Cyclohexanecarboxylic Acids, Disease Models, Animal, Fear, Female, Male, Memory Disorders, Motor Activity, Sex Characteristics, Receptors, Metabotropic Glutamate, Mice, Knockout, Maze Learning, Gait Disorders, Neurologic, Rotarod Performance Test, Mice
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