Diminished potassium-stimulated GABA release in vivo in genetically epilepsy-prone rats

This experiment was conducted to assess the physiological relevance of observed changes in transmitter amino acid content in severe seizure genetically epilepsy-prone rats (GEPR-9s) by use of microdialysis. Adult male GEPR-9s and non-epileptic control rats were implanted with guide cannulae, and 6 mm (loop) dialysis probes were inserted unilaterally into rostral caudate and perfused with artificial cerebrospinal fluid. Each subject was perfused in the awake state with 100 or 150 mM K+ for 80 min in separate counterbalanced sessions, and 20-min fractions collected. High K+ perfusion increased extracellular fluid GABA and glutamate (GLU) in a concentration-dependent manner in both GEPR-9s and non-epileptic control rats. However, in the presence of 150 mM K+ GABA release was decreased in GEPR-9s relative to controls throughout the stimulation interval. In contrast, the increase in extracellular fluid GLU after high K+ was not different in the two groups. These results suggest an important role for mechanisms underlying GABA release in the seizure susceptibility observed in GEPR-9s.