mGlu5 receptor deletion does not confer seizure protection to mice.
Metabotropic glutamate mGlu5 receptors have been implicated in the regulation of seizures and have been suggested as a target against which discovery of novel anticonvulsants may be possible. However, the experimental literature is not consistent in reporting anticonvulsant efficacy of mGlu5 receptor antagonists. Additional assessment of this target was approached in the present study by comparing convulsions in wild-type (WT) and mGlu5 receptor null (knockout or KO) mice. Chemically induced seizures induced by a variety of mechanisms including pentylenetetrazole, N-methyl-d-aspartic acid (NMDA), cocaine, kainic acid, aminophylline, 4-aminopyridine, strychnine, and nicotine did not differentially increase clonic, clonic/tonic, or lethality in WT vs. mGlu5 receptor KO mice. The mGlu5 receptor antagonist 3-[(2-Methyl-1,3-thiazol-4-yl) ethynyl]-pyridine (MTEP) did not significantly prevent seizures induced by NMDA; in contrast, the uncompetitive NMDA receptor antagonist, dizocilpine, significantly prevented NMDA-induced seizures and lethality in both WT and KO mice. The present findings do not support the idea that mGlu5 receptors play as important a role in seizure control as previously speculated.
Witkin
Jeffrey M
JM
Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Baez
Melvyn
M
Yu
Jianliang
J
Eiler
William J A
WJ
D000818:Animals; D003292:Convulsants / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000517:prevention & control*
D003292:Convulsants; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate