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Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7

Sansig, G. and Bushell, T. and Clarke, V.R. and Rozov, A. and Burnashev, N. and Portet, C. and Gasparini, F. and Schmutz, M. and Klebs, K. and Shigemoto, R. and Flor, P.J. and Kuhn, R. and Knoepfel, T. and Schroeder, M. and Hampson, D.R. and Collett, V.J. and Zhang, C. and Duvoisin, R.M. and Collingridge, G.L. and van der Putten, Herman (2001) Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience, 21 (22). pp. 8734-8745. ISSN 0270-6474

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Abstract

To study the role of mGlu7 receptors (mGluR7), we used homologous recombination to generate mice lacking this metabotropic receptor subtype (mGluR7-/-). After the serendipitous discovery of a sensory stimulus-evoked epileptic phenotype, we tested two convulsant drugs, pentylenetetrazole (PTZ) and bicuculline. In animals aged 12 weeks and older, subthreshold doses of these drugs induced seizures in mGluR7-/-, but not in mGluR7+/-, mice. PTZ-induced seizures were inhibited by three standard anticonvulsant drugs, but not by the group III selective mGluR agonist (R,S)-4-phosphonophenylglycine (PPG). Consistent with the lack of signs of epileptic activity in the absence of specific stimuli, mGluR7-/- mice showed no major changes in synaptic properties in two slice preparations. However, slightly increased excitability was evident in hippocampal slices. In addition, there was slower recovery from frequency facilitation in cortical slices, suggesting a role for mGluR7 as a frequency-dependent regulator in presynaptic terminals. Our findings suggest that mGluR7 receptors have a unique role in regulating neuronal excitability and that these receptors may be a novel target for the development of anticonvulsant drugs.

Item type: Article
ID code: 5463
Keywords: epilepsy, mGluR7, knock-out, mice, group III mGluR, (R, S)-4-phosphonophenylglycine, pharmacology, Pharmacy and materia medica, Physiology, Neuroscience(all)
Subjects: Medicine > Pharmacy and materia medica
Science > Physiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 05 Mar 2008
    Last modified: 04 Sep 2014 14:31
    URI: http://strathprints.strath.ac.uk/id/eprint/5463

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