Seizure development in kindling fast and kindling slow rat strains


Dufresne, Carolynn (Carolynn Mary)




It is evident that some forms of epilepsy are mediated by genetic factors. Experimental models, based on the susceptibility to various seizure provoking stimuli, have been developed to examine the underlying mechanisms of genetically determined seizure disorders. One such model is based on the susceptibility to amygdala kindling stimulation in two selectively bred rat strains. In the present study, kindling FAST and kindling SLOW rat strains were shown to exhibit differences in the development and subsequent manifestation of amygdala kindled seizures. SLOW animals required far more stimulations than FAST animals to elicit the first stage 5 generalized seizure. The behavioral responses associated with these generalized seizures were markedly different for the two strains. Partial seizure development was also significantly retarded in the SLOW strain compared to the FAST strain. Differences were further evident after partial seizures were developed. While SLOW animals exhibited protracted partial seizures over many trials, partial seizures in FAST animals were elicited on only a few trials before generalized seizures were developed. Additional strain differences were observed in the manifestation of spontaneous interictal spikes (IIS). IISs were seen only in the SLOW strain and appeared to correlate positively with kindling development; i.e., higher kindling scores were associated with a higher frequency of IISs. Finally, norepinephrine (NE) levels in naive animals were found to be higher in the SLOW strain compared to the FAST strain. Taken together, the results suggest that strain differences are related to the efficacy of inhibitory systems. In the SLOW strain, it appears that recruitment of seizure and/or access to pathways triggering convulsive behavior is inhibited, resulting in low susceptibility to amygdala kindling stimulation.


Kindling (Neurology)




Carleton University

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