THE ONTOGENY OF [H-3] GAMMA-HYDROXYBUTYRATE AND [H-3] GABA(B) BINDING-SITES - RELATION TO THE DEVELOPMENT OF EXPERIMENTAL ABSENCE SEIZURES

gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound which has the ability to induce generalized absence seizures when given to animals. There is growing evidence that both gamma-aminobutyric acid (GABA)(B)- and GHB-mediated mechanisms are involved in the pathogenesis of this phenomenon. Because of the fact that absence seizures are a disorder of children the ontogeny of [H-3]GHB and[H-3]GABA(B) binding and the developmental appearance of absence seizures in the GHB model of absence was ascertained and compared in developing rats. [H-3]GABA(B) binding was present within the first 3 days of postnatal life and rose to levels which exceeded those found in adults, peaking between the 3rd and 5th postnatal week. [H-3]GHB binding on the other hand did not appear until postnatal day 17 when it was detectable in the CA1 region of the hippocampus. There was a steady increase in [H-3]GHB binding until adult levels were reached by postnatal day 40. Comparison of [H-3]GABA(B) and [H-3]GHB binding revealed that both sites were common to layer I-III of cortex, but otherwise differed in their regional distribution. There was an absolute concordance of the ontogeny of GHB-induced absence seizures with the developmental appearance of [H-3]GHB binding in the superficial laminae of cortex; both appeared at postnatal day 18. These data support the hypotheses that the [H-3]GHB and [H-3]GABA(B) binding sites are separate from one another and suggest that maturational events in thalamus and cortex in the 3rd postnatal week are involved in the expression of GHB-induced absence seizures.