γ-Hydroxybutyric acid induced spike and wave discharges in rats: Relation to high-affinity [ 3H]γ-hydroxybutyric acid binding sites in the thalamus and cortex

Abstract

γ-Hydroxybutyric acid is a naturally occurring compound which induces bilaterally synchronous spike and wave discharges in rats. The γ-hydroxybutyric acid model of absence seizures simulates clinical absence seizures behaviorally as well as electrographically. The present study was undertaken in order to establish the role of the high-affinity γ-hydroxybutyric acid binding sites in the generation of γ-hydroxybutyric acid-induced spike and wave discharges. Spike and wave discharges induced by γ-hydroxybutyric acid were recorded with the aid of bipolar depth electrodes implanted in discrete regions of thalamus, cortex and hippocampus. In the present study we found that ventroposterolateral, 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, whereas no spike and wave discharges were recorded from deeper layers (V–VI) of frontoparietal cortex. At the onset of spike and wave discharges induced by γ-hydroxybutyric acid, a rapid but reversible upregulation of γ-hydroxybutyric acid binding sites was observed. This increased [ 3H]γ-hydroxybutyric acid binding was characterized by an increase in the number of γ-hydroxybutyric acid sites with no significant change in their affinity for γ-hydroxybutyric acid. Moreover, the change in [ 3H]γ-hydroxybutyric acid binding was observed only in those thalamic structures and cortical layers which were found to be involved in the generation of spike and wave discharges induced by γ-hydroxybutyric acid. The CA3 field or dorsal hippocampus possesses the highest density of [ 3H]γ-hydroxybutyric acid binding sites of all brain regions. However, no significant change in [ 3H]γ-hydroxybutyric acid binding was observed in this region nor was the CA3 field involved in the generation of spike and wave discharges during γ-hydroxybutyric acid-induced absence-like seizures. These findings confirm that γ-hydroxybutyric acid-induced absence-like seizures originate from thalamocortical pathways and that the onset of γ-hydroxybutyric acid-induced spike and wave discharges is directly related to the regulation of γ-hydroxybutyric acid binding sites in those regions which constitute the involved thalamocortical loop.