Selective mGluR5 antagonism attenuates the stress-induced reduction of MK-801's antiseizure potency in the genetically inbred Balb/c mouse.

Abstract

The ability of MK-801 (dizocilpine), a noncompetitive N-methyl D-aspartate (NMDA) antagonist, to antagonize electrical seizures is reduced in stressed mice. Stress-associated alterations in seizure susceptibility and diminished efficacy of antiseizure medications in humans have been reported [Joëls, 2009; Haut et al., 2007; Moshe et al., 2008]; thus, these experimental observations implicate altered endogenous tone of NMDA receptor-mediated neurotransmission in clinically adverse effects of stress on seizure proneness and treatment. The current exploratory experiment examined the effect of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of mGluR5, administered prior to stress on the stress-induced reduction of MK-801's antiseizure effect in Swiss-Webster and Balb/c mice; the Balb/c mouse is behaviorally hypersensitive to MK-801. Interestingly, the data suggest that MPEP can attenuate the severity of the stress-induced reduction of MK-801's antiseizure effect in the Balb/c strain. Thus, mGluR5 could serve as a target for strategies for adjuvant treatment of seizures exacerbated by stress.

• Authors: Stephen I Deutsch, Jessica A Burket, William R Cannon, Luis F Jacome
• Journal: Epilepsy & behavior : E&B (Epilepsy Behav) Vol. 21 Issue 4 Pg. 352-5 (Aug 2011) ISSN: 1525-5069 [Electronic] United States
• PMID: 21683659 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• GRM5 protein, human
• Grm5 protein, mouse
• Pyridines
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate
• Dizocilpine Maleate
• 6-methyl-2-(phenylethynyl)pyridine

Topics

• Animals
• Dizocilpine Maleate (pharmacology, therapeutic use)
• Electroshock
• Male
• Mice
• Mice, Inbred BALB C
• Pyridines (pharmacology, therapeutic use)
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate (antagonists & inhibitors)
• Seizures (drug therapy, physiopathology)
• Stress, Physiological (physiology)
• Stress, Psychological (physiopathology)