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Keywords:

  • Fenfluramine;
  • Serotonin;
  • Entorhinal cortex;
  • Low-Mg2+-induced epileptiform activity;
  • Paroxetine

Summary: Purpose: The entorhinal cortex (EC) represents the main input structure to the hippocampus and seems to be critically involved in temporal lobe epilepsy. 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 epilepsy.

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 investigated the effect of bath-applied FFA (200 μmol/L to 1 mmol/L) on epileptiform activity induced by omitting MgSO4 from the artificial cerebrospinal fluid.

Results: We demonstrate that FFA reversibly blocks epileptiform activity in the EC. Surprisingly, in the presence of the 5-HT uptake blocker paroxetine, the FFA-induced effect was diminished. Coapplication of the 5-HTIA receptor antagonist WAY 100635 prevented the FFA-induced anticonvulsive effect, suggesting that (a) the FFA-induced suppression of epileptiform activity is mediated by the release of 5-HT from synaptic terminals within the EC rather than by an unspecific effect of FFA and (b) released 5-HT most likely blocks the activity by activation of 5-HTIA receptors.

Conclusion: FFA, which is primarily used because of its anorectic activity, might get an additional therapeutic value in the treatment of temporal lobe epilepsy with parahippocampal involvement.