Induction of audiogenic seizures in normal and genetically epilepsy-prone rats following focal microinjection of an excitant amino acid into reticular formation and auditory nuclei.
An excitant amino acid (EAA), N-methyl-D-aspartate (NMDA), induces susceptibility to seizures when bilaterally microinjected into subcortical auditory nuclei of normal rats. Thirty-five percent of animals exhibit only audiogenic seizures (AGS) after infusions of NMDA into inferior colliculus (IC). Infusions into cochlear nucleus and medial geniculate body never produce susceptibility to AGS without non-audiogenic seizures (N-AGS). The overall seizure incidence (AGS and N-AGS) with IC infusions is 100%, but the incidence is less than 50% with infusions into cochlear nucleus or medial geniculate body. Although AGS susceptibility is induced by NMDA infusions in normal animals, the seizures are submaximal in severity and lack tonic components. Bilateral infusions of NMDA into IC or reticular formation of the substrain of genetically epilepsy-prone rats (GEPRs) that exhibits submaximal AGS (GEPR-3s) do not increase seizure severity. These data along with studies showing increased EAA levels and excitotoxic-like damage in the IC of the GEPR and blockade of AGS with an EAA receptor antagonist or synthesis inhibitor suggest that an EAA in the IC is involved in initiation of AGS in the GEPR. However, EAA action in the GEPR IC is not sufficient to induce the complete spectrum of seizure behaviors, and additional mechanisms may be required for induction of maximal severity audiogenic seizures.
Faingold
C L
CL
Dept. of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-9230.
Millan
M H
MH
Boersma Anderson
C A
CA
Meldrum
B S
BS
D000161:Acoustic Stimulation; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D005829:Geniculate Bodies / Q000187:drug effects / Q000503:physiopathology; D007245:Inferior Colliculi / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D012154:Reticular Formation / Q000187:drug effects / Q000503:physiopathology*
D001224:Aspartic Acid; D016202:N-Methylaspartate