Glutamatergic activation of the amygdala differentially mimics the effects of audiogenic seizure kindling in two substrains of genetically epilepsy-prone rats.
Comparisons of neuronal network mechanisms in closely related inherited seizure models are providing novel insights into epileptogenic pathophysiology. Genetically epilepsy-prone rats (GEPRs) exist in two substrains that inherit long-term susceptibility to behaviorally distinct audiogenic seizures (AGS). GEPR-3s exhibit generalized clonic AGS, while GEPR-9s exhibit generalized tonic AGS. After AGS kindling the tonic AGS of GEPR-9s is followed by generalized posttonic clonus (PTC), while the generalized clonic AGS is followed by facial and forelimb (F&F) clonus in GEPR-3s. PTC and F&F clonus are very rare in GEPRs before AGS kindling. The neuronal network subserving AGS in GEPR-9s lies exclusively in brainstem sites, but amygdala (AMG) and other sites are recruited into the network after AGS kindling. The present study attempted to mimic the effects of AGS kindling by bilaterally microinjecting subconvulsive doses of N-methyl-D-aspartate (NMDA) into the AMG of nonkindled GEPRs. NMDA (10 nmol/side) microinjected into AMG reversibly induced susceptibility to F&F clonus immediately following generalized clonic AGS in most nonkindled GEPR-3s. NMDA (7.5 nmol/side), microinjected into AMG temporarily induced susceptibility to generalized PTC immediately following tonic AGS in most nonkindled GEPR-9s. No seizures were induced in normal rats by these treatments, and no seizures were seen in GEPRs with these NMDA doses except those induced by acoustic stimuli. These findings support a critical role in AGS kindling for the AMG in the neuronal networks for both forms of AGS. However, the behavioral effect of the treatment was different in the two AGS substrains, suggesting interrelated but not identical pathophysiological mechanisms in these closely related epilepsy models.
Raisinghani
M
M
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794-9629, USA.
Feng
H J
HJ
Faingold
Carl L
CL
D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000378:metabolism*; D007696:Kindling, Neurologic; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*
D018698:Glutamic Acid; D016202:N-Methylaspartate