ENDOGENOUS SEROTONIN INHIBITS EPILEPTIFORM ACTIVITY IN RAT HIPPOCAMPAL CA1 NEURONS VIA 5-HYDROXYTRYPTAMINE(1A) RECEPTOR ACTIVATION

The modulatory effects of endogenous serotonin on the synaptic transmi ssion and epileptiform activity were studied in the rat hippocampus wi th the use of extracellular and intracellular recording techniques. Fi eld excitatory postsynaptic potential was reversibly depressed by sero tonin in a concentration-dependent manner. Intracellular recordings re vealed that serotonin-mediated synaptic depression was unaffected by e xtracellular Ba2+ or intracellular application df Cs+ while the postsy naptic hyperpolarizing effect was completely blocked. Epileptiform act ivity induced by picrotoxin (50 mu M), a GABA(A), receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5-hydroxytryptamine(1A),, agonist and was block ed by 5-hydroxytryptamine(1A),. antagonists. 5-Hydroxytryptamine(2), a ntagonist had no effect on the modulation. Similarly, fluoxetine, a se lective serotonin re-uptake blocker, potently inhibited the epileptifo rm activity and this effect was blocked by 5-hydroxytryptamine(1A),. r eceptor antagonist. Depletion of endogenous serotonin by pretreating t he slices with p-chloroamphetamine completely prevented the antiepilep tic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action o f fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine(1A),, receptor. Endogenous se rotonin transmission in the hippocampus is therefore capable of limiti ng the development and propagation of seizure activity. (C) 1998 IBRO. Published by Elsevier Science Ltd.