GAMMA-HYDROXYBUTYRIC ACID-INDUCED SPIKE AND WAVE DISCHARGES IN RATS -RELATION TO HIGH-AFFINITY [H-3] GAMMA-HYDROXYBUTYRIC ACID-BINDING SITES IN THE THALAMUS AND CORTEX

Gamma-hydroxybutyric acid is a naturally occurring compound which indu ces bilaterally synchronous spike and wave discharges in rats. The gam ma-hydroxybutyric acid model of absence seizures simulates clinical ab sence seizures behaviorally as well as electrographically. The present study was undertaken in order to establish the role of the high-affin ity gamma-hydroxybutyric acid binding sites in the generation of gamma -hydroxybutyric acid-induced spike and wave discharges. Spike and wave discharges induced by gamma-hydroxybutyric acid were recorded with th e aid of bipolar depth electrodes implanted in discrete regions of tha lamus, cortex and hippocampus. In the present study we found that vent roposterolateral, ventroposteromedial, medial and the reticular nuclei of the thalamus discharged synchronously with the cortical generation of spike and wave discharges. In the cortex, the superficial layers ( I-IV) of frontoparietal cortex generated spike and wave discharges, wh ereas no spike and wave discharges were recorded from deeper layers (V -VI) of frontoparietal cortex. At the onset of spike and wave discharg es induced by gamma-hydroxybutyric acid, a rapid but reversible upregu lation of gamma-hydroxybutyric acid binding sites was observed. This i ncreased [H-3]gamma-hydroxybutyric acid binding was characterized by a n increase in the number of gamma-hydroxybutyric acid sites with no si gnificant change in their affinity for gamma-hydroxybutyric acid. More over, the change in [H-3]gamma-hydroxybutyric acid binding was observe d only in those thalamic structures and cortical layers which were fou nd to be involved in the generation of spike and wave discharges induc ed by gamma-hydroxybutyric acid. The CA3 field or dorsal hippocampus p ossesses the highest density of [H-3]gamma-hydroxybutyric acid binding sites of all brain regions. However, no significant change in [H-3]ga mma-hydroxybutyric acid binding was observed in this region nor was th e CA3 field involved in the generation of spike and wave discharges du ring gamma-hydroxybutyric acid-induced absence-like seizures. These fi ndings confirm that gamma-hydroxybutyric acid-induced absence-like sei zures originate from thalamocortical pathways and that the onset of ga mma-hydroxybutyric acid-induced spike and wave discharges is directly related to the regulation of gamma-hydroxybutyric acid binding sites i n those regions which constitute the involved thalamocortical loop.