The ontogeny of [3H]gamma-hydroxybutyrate and [3H]GABAB binding sites: relation to the development of experimental absence seizures

Brain Res. 1994 Oct 3;659(1-2):147-56. doi: 10.1016/0006-8993(94)90874-5.

Abstract

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 [3H]GHB and [3H]GABAB binding and the developmental appearance of absence seizures in the GHB model of absence was ascertained and compared in developing rats. [3H]GABAB 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. [3H]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 [3H]GHB binding until adult levels were reached by postnatal day 40. Comparison of [3H]GABAB and [3H]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 [3H]GHB binding in the superficial laminae of cortex; both appeared at postnatal day 18. These data support the hypotheses that the [3H]GHB and [3H]GABAB 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Butyrolactone / pharmacology
  • Animals
  • Animals, Newborn / growth & development*
  • Animals, Newborn / metabolism*
  • Binding Sites
  • Electrophysiology
  • Epilepsy, Absence / chemically induced
  • Epilepsy, Absence / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Oxybate / metabolism*
  • Tritium
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Tritium
  • gamma-Aminobutyric Acid
  • Sodium Oxybate
  • 4-Butyrolactone