title: Kindled seizures result in decreased responsiveness of benzodiazepine receptors to gamma-aminobutyric acid (GABA).
abstract: Repeated kindled seizures result in increased numbers of benzodiazepine receptors in fascia dentata membranes. Our previous work localized these receptors to a discrete neuronal population, the dentate granule cells. The present investigation characterizes the regulation of this binding by NaCl, pentobarbital and gamma-aminobutyric acid (GABA). [3H]Flunitrazepam binding in membranes from kindled rats exceeded that from controls by 24%. NaCl increased this binding in membranes prepared from control and kindled animals by roughly equivalent amounts (18 and 14%, respectively). No significant differences were found in the effects of pentobarbital on benzodiazepine binding between kindled and control groups. In contrast, addition of GABA increased benzodiazepine binding by a significantly smaller percentage in the kindled (116 +/- 5%) compared to the control (138 +/- 11%) group. We propose that this altered molecular response to GABA is intimately related to the enhanced GABA-mediated inhibition of granule cells present after kindled seizures.
mesh_terms: D000818:Animals; D005445:Flunitrazepam / Q000378:metabolism; D007696:Kindling, Neurologic; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D012640:Seizures / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D010424:Pentobarbital