KINDLING INDUCES TIME-DEPENDENT AND REGIONAL SPECIFIC CHANGES IN THE [H-3] MUSCIMOL BINDING IN THE RAT HIPPOCAMPUS - A QUANTITATIVE AUTORADIOGRAPHIC STUDY
Mng. Titulaer et al., KINDLING INDUCES TIME-DEPENDENT AND REGIONAL SPECIFIC CHANGES IN THE [H-3] MUSCIMOL BINDING IN THE RAT HIPPOCAMPUS - A QUANTITATIVE AUTORADIOGRAPHIC STUDY, Neuroscience, 59(4), 1994, pp. 817-826
To investigate possible changes in the GABA, receptor agonist site in
the CAI area and fascia dentata of rats kindled by stimulation of Scha
ffer collaterals, a quantitative autoradiographic study of the [H-3]mu
scimol binding was carried out. Two kindled groups were studied, at 24
h (fully kindled stage) and at 28 days (long-term stage) after the la
st 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 th
e complete range of tested [H-3]muscimol concentrations was significan
tly increased by 30-50% in the fascia dentata, while the binding was s
ignificantly decreased by 10-25% in the CA1 area. The high/intermediat
e-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 epileptogene
sis induces long-lasting changes in the GABA(A) receptor agonist bindi
ng sites that are region specific. We hypothesize that the changes enc
ountered at the fully kindled stage, i.e. increased binding in the fas
cia dentata and decreased binding in the CA1 area, may underly the ele
ctrophysiologically observed increased paired-pulse depression of fiel
d potentials in the former and the decreased paired-pulse depression i
n the latter area [Kamphuis et al. (1992) Neurosci. Lett. 141, 101-105
; Kamphuis et al. (1988) Blain Res, 440, 205-215; Zhao and Leung (1991
) Brain Res. 564, 220-229; Zhao and Leung (1992) Brain Res. 582, 163-1
67]. 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.