Lothman E W, Perlin J B, Salerno R A
Department of Neurology, University of Virginia Medical Center, Charlottesville 22908.
Epilepsy Res. 1988 Nov-Dec;2(6):356-66. doi: 10.1016/0920-1211(88)90047-2.
Previous work has shown that closely spaced stimuli can activate short-term and long-term inhibitory processes that suppress kindling and the expression of kindled responses. The present experiments employed stimulus trains of longer duration than traditionally used in kindling work. Hippocampal seizures were triggered in rats at rates considerably faster than those reported to activate these inhibitory processes. Such rapidly recurring hippocampal seizures (RRHS) promptly led to a persistent, fully kindled state in which consistent kindled motor responses, constant duration electrographic seizures and stable afterdischarge thresholds were present. These kindled responses could be elicited every 30 min for 6-8 h/day on an alternate day schedule, but the kindled responses depended on delivery of supramaximal stimuli. Extending the number of RRHS on a given test day led to the appearance of a slowly developing but enduring suppression of kindled responses and an elevation of afterdischarge thresholds. Restricting the study period to 6 h on a given day, but using a consecutive instead of alternate day schedule, also led to a long-duration suppression of kindled responses. These results show that the short-duration inhibitory processes associated with kindled seizures can be more easily overcome than long-duration processes. The latter seem to involve an elevation of afterdischarge thresholds. The experiments also establish procedures by which detailed investigations of the effects of experimental manipulations on kindled responses can be examined.