Roles of neurotransmitter amino acids in seizure severity and experience in the genetically epilepsy-prone rat

This investigation was designed to compare seizure-naive and seizure-experienced genetically epilepsy-prone rats (GEPRs) in order to distinguish transmitter amino acid changes related to seizure severity from those associated with seizure experience. Moderate (GEPR-3) and severe (GEPR-9) seizure male GEPRs were divided into seizure-naive and seizure-experienced groups based on whether seizure-inducing acoustical stimuli had been presented between 45 and 60 days of age, and then were sacrificed at 76 +/- 3 days. gamma-Aminobutyric acid (GABA) concentrations were lower in both GEPR-3s and GEPR-9s compared to non-epileptic controls in each brain region examined. Aspartate content was elevated in 5 of 6 brain areas in GEPR-9s compared to non-epileptic controls, and in 3 regions was higher in GEPR-9s than in GEPR-3s. In contrast, taurine concentrations were higher in GEPR-3s than in non-epileptic controls in each region, and in 4 areas were higher in GEPR-3s than in GEPR-9s. Changes resulting from seizure experience consisted of increases in aspartate, glutamate and glycine in seizure-experienced compared to seizure-naive groups in inferior colliculus and in motor-sensory and frontal cortices. These findings suggest that the high levels of taurine in GEPR-3s and the elevated content of aspartate in GEPR-9s have roles as determinants of seizure severity. The low concentrations of GABA in both types of GEPRs are consistent with a role for this amino acid in determination of seizure susceptibility. Furthermore, the seizure-induced changes in aspartate and glutamate in both types of GEPRs support the concept that these excitatory amino acids mediate changes in seizure predisposition.(ABSTRACT TRUNCATED AT 250 WORDS)