Purpose: The entorhinal cortex (EC) represents the main input structure to
the hippocampus and seems to be critically involved in temporal lobe epilep
sy. Considering that the EC receives a strong serotonergic projection from
the raphe nuclei and expresses a high density of serotonin (5-HT) receptors
, the effect of the 5-HT-releasing drug fenfluramine (FFA) on epileptiform
activity generated in the EC was investigated in an in vitro model of epile
psy.
Methods: The experiments were performed on 43 horizontal slices containing
the EC, the subiculum, and the hippocampal formation obtained from 230-250
g adult Wistar rats. Using extracellular recording techniques, we investiga
ted the effect of bath-applied FFA (200 mu mol/L to 1 mmol/L) on epileptifo
rm activity induced by omitting MgSO4 from the artificial cerebrospinal flu
id.
Results: We demonstrate that FFA reversibly blocks epileptiform activity in
the EC. Surprisingly, in the presence of the 5-HT uptake blocker paroxetin
e, the FFA-induced effect was diminished. Coapplication of the 5-HT1A recep
tor antagonist WAY100635 prevented the FFA-induced anticonvulsive effect, s
uggesting that (a) the FFA-induced suppression of epileptiform activity is
mediated by the release of 5-HT from synaptic terminals within the EC rathe
r than by an unspecific effect of FFA and (b) released 5-HT most likely blo
cks the activity by activation of 5-HT1A receptors.
Conclusion: FFA, which is primarily used because of its anorectic activity,
might get an additional therapeutic value in the treatment of temporal lob
e epilepsy with parahippocampal involvement.