Increased gamma-hydroxybutyric acid receptors in thalamus of a genetic animal model of petit mal epilepsy.

The distribution and kinetics of specific binding sites for gamma-hydroxybutyrate (GHB), a naturally occurring compound known to produce absence-like seizures, was studied in the brains of Wistar rats with spontaneous, bilaterally synchronous spike wave discharges (SWDs), a model of petit mal epilepsy, and non-epileptic controls using [3H]GHB autoradiography. [3H]GHB receptor binding was increased 40-60% in lateral thalamic nuclei of the epileptic animals. Kinetic analysis showed that the increase in the binding was due to an increase in density of low affinity GHB binding sites in the epileptic animals. Given the ability of GHB to produce petit mal-like seizures when administered to animals, and the fact that the SWDs in the Wistar rat model seem to emanate from lateral thalamus, these data raise the possibility that GHB-mediated mechanisms may play a role in the pathogenesis of petit mal seizures.