Serotonin releasers modulate reactivity of the rat hippocampus to afferent stimulation.

Electrical stimulation of the perforant path produces a characteristic population EPSP and population spike in the dentate gyrus of the anesthetized rat. Parenteral administration of a serotonin releasing drug D-fenfluramine (FFA) caused a marked (30-100%) and highly significant increase in dentate gyrus population spike response to perforant path stimulation without affecting the slope of the population excitatory postsynaptic potential (EPSP). This indicates that FFA modifies granular cell excitability to afferent stimulation. The facilitatory effect of FFA was not present in rats depleted of serotonin following treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) but was restored after restoration of serotonin synthesis with the precursor 5-hydroxytryptophan indicating that presence of serotonin in terminals is required for the action of FFA.