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

Epilepsy Behav. 2011 Aug;21(4):352-5. doi: 10.1016/j.yebeh.2011.03.026. Epub 2011 Jun 16.

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.

MeSH terms

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

Substances

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