Kindled seizures result in decreased responsiveness of benzodiazepine receptors to gamma-aminobutyric acid (GABA)
Fanelli, R.J.; Mcnamara, J.O.
Journal of Pharmacology and Experimental Therapeutics 226(1): 147-150
1983
ISSN/ISBN: 0022-3565 PMID: 6306222 Document Number: 201313
Repeated kindled seizures result in increased numbers of benzodiazepine receptors in fascia dentata membranes. Previous work localized these receptors to a discrete neuronal population, the dentate granule cells. The regulation of this binding by NaCl, pentobarbital and GABA was characterized. [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. Addition of GABA increased benzodiazepine binding by a significantly smaller percentage in the kindled (116 .+-. 5%) compared to the control (138 .+-. 11%) group. Evidently this altered molecular response to GABA is intimately related to the enhanced GABA-mediated inhibition of granule cells present after kindled seizures.