Kindling induces time-dependent and regional specific changes in the [ 3h]muscimol binding in the rat hippocampus: A quantitative autoradiographic study

Abstract

To investigate possible changes in the GABA A receptor agonist site in the CA1 area and fascia dentata of rats kindled by stimulation of Schaffer collaterals, a quantitative autoradiographic study of the [ 3H]muscimol binding was carried out. Two kindled groups were studied, at 24 h (fully kindled stage) and at 28 days (long-term stage) after the last class V seizure. Several concentrations of [ 3H]muscimol were tested in the range of the high/intermediate (5–40 nM) and low-affinity (60–100 nM) binding sites. In the fully kindled group, the binding over the complete range of tested [ 3H]muscimol concentrations was significantly increased by 30–50% in the fascia dentata, while the binding was significantly decreased by 10–25% in the CA1 area. The high/intermediate-affinity binding was still significantly increased by 20–30% in the fascia dentata 28 days after the last seizure. In this long-term group there was still a significant decrease of 10–18% of the low-affinity binding in the CA1 area. These results show that kindling epileptogenesis induces long-lasting changes in the GABA A receptor agonist binding sites that are region specific. We hypothesize that the changes encountered at the fully kindled stage, i.e. increased binding in the fascia dentata and decreased binding in the CA1 area, may underly the electrophysiologically observed increased paired-pulse depression of field potentials in the former and the decreased paired-pulse depression in the latter area [ Kamphuis et al. (1992) Neurosci. Lett. 141, 101–105; Kamphuis et al. (1988) Brain Res. 440, 205–215; Zhao and Leung (1991) Brain Res. 564, 220–229; Zhao and Leung (1992) Brain Res. 582, 163–167]. We conclude that the observed changes may not only contribute to the induction of kindling epileptogenesis but may also play a role in the maintenance of the kindled state.