Differences in kindling development in seven outbred and inbred rat strains

The kindling phenomenon, i.e., the progressive development of focal and sec ondarily generalized seizures upon repeated electrical stimulation of a lim bic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, d ifferences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences ar e thought to be involved in this variability. In most studies on kindling i n rats, outbred strains such as Sprague-Dawley have been used. In the prese nt study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar- Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the ste pwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was deter mined before and after kindling. Once daily electrical stimulation of the b asolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest numb er of stimulations to reach fully kindled (stage 5) seizures, and Lewis rat s showing the highest number of the 7 strains. In contrast to the significa nt differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not s ignificantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked difference s in ADD of a stage 5 seizure were obtained between strains, with strains k indling rapidly exhibiting longer ADD than strains kindling slowly. Postkin dling afterdischarge threshold (ADT) varied significantly among strains, bu t only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial p hase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predomin antly due to the time needed to progress hom stage 1 to subsequent stages o f the kindling process. The data seem to indicate that inbred rat strains o ffer an interesting resource for dissecting the underlying genetic basis fo r phenotypic differences in epileptogenesis as induced by kindling, althoug h the high variability of kindling rates seen within some inbred strains we akens this possibility. (C) 1998 Academic Press.