Abstracts

Kindling is a progressive increase in seizure activity following the daily application of focal, low-intensity electrical stimulation of different forebrain regions. Two strains of rats were developed to exhibit different rates of amygdala kindling, and were called Fast and Slow kindlers. These animals also show different response profiles to [alpha]2-adrenoreceptor (AR) agonists. Therefore, the objective of this work was to examine [alpha]2-AR binding sites and subtype mRNA expression in the CNS of naive Fast and Slow rats., [alpha]2-AR binding sites were measured in naive Fast (n=8) and Slow (n=8) kindlers with the [alpha]2-AR antagonist [[sup3]H]RX821002. [alpha]2-AR binding sites were measured in the locus coeruleus (LC), neocortex, bed nucleus of the stria terminalis, thalamus, septum, amygdala, habenula and hippocampus. [alpha]2-AR is composed of three different subtypes. [alpha]2A- and [alpha]2C-AR mRNA were determined in the CNS of Fast and Slow kindlers by in situ hybridization with oligonucleotides. [alpha]2A-AR mRNA was measured in the LC, cortex, septum, hypothalamus and amygdala, and [alpha]2C-AR mRNA was measured in the LC, cortex, hippocampus, amygdala, cerebellum, caudate and nucleus accumbens., [alpha]2-AR binding sites, as determined by [[sup3]H]RX821002, were not statistically different between Fast and Slow kindlers in all regions of the CNS. [alpha]2A-AR mRNA expression, the subtype responsible for [[sup3]H]RX821002 binding, therefore, was not different. However, [alpha]2C-AR mRNA expression was different between Fast and Slow kindlers in many regions of the CNS, including nucleus accumbens, dentate gyrus granule cell layer, cingulate gyrus, cerebellum and neocortex layer II: in these cases, [alpha]2C-AR mRNA expression was significantly elevated in the Slow compared to Fast kindlers., These data indicate a signifcant increase in several brain structures in the [alpha]2C-AR mRNA expression in Slow versus the Fast kindlers. These differences in [alpha]2C-AR mRNA may explain the different [alpha]2 adrenergic pharmacological profiles between the two strains, and speak additionally to adrenergic involvement in epileptogenesis., (Supported by VA Puget Sound health Care Center and CIHR.)