title: 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.affiliation: Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507–1912, USA. deutscsi@evms.edu
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Deutsch
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Burket
authors.forename: William R
authors.initials: WR
authors.lastname: Cannon
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jacome
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use*; D004597:Electroshock; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016291:Dizocilpine Maleate; C121465:6-methyl-2-(phenylethynyl)pyridine