Intracerebral 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) produces limbic seizures that are not blocked by ionotropic glutamate receptor antagonists.
The functional role of metabotropic glutamate receptor (mGluR) activation was investigated following intracerebral administration of 1S,3R-ACPD in mice. Injections of 1S,3R-ACPD (50-800 nmol in 5 microliters) into the thalamus produced a dose-dependent increase in limbic seizures. These effects were stereoselective since 1R,3S-ACPD, did not elicit seizure activity. Pharmacologically, limbic seizures were attenuated by the mGluR partial agonist/antagonist L-2-amino-3-phosphonopropionate (L-AP3) and dantrolene, an inhibitor of intracellular calcium mobilization, but not by D-AP3 or ionotropic glutamate receptor antagonists (MK-801 or GYKI-52466). Thus, activation of mGluRs by 1S,3R-ACPD in mice, induces limbic seizures that may involve the mobilization of intracellular calcium stores.
Tizzano
J P
JP
Toxicology Research Division, Lilly Research Laboratories Eli Lilly and Company, Greenfield, IN 46140.
Griffey
K I
KI
Johnson
J A
JA
Fix
A S
AS
Helton
D R
DR
Schoepp
D D
DD
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003515:Cycloleucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000033:anatomy & histology; D007267:Injections; D008032:Limbic System / Q000502:physiology*; D008297:Male; D051379:Mice; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D013788:Thalamus / Q000033:anatomy & histology
D000927:Anticonvulsants; D017459:Receptors, Amino Acid; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane