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The effects of the serotonin (5-HT)3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), were studied in CA1 pyramidal cells of the rat hippocampus in vitro using the whole cell gigaseal technique. 2-Methyl-5-HT (10 and 50 microM) did not change significantly the electrophysiologic properties of the cells but reversibly reduced excitatory and inhibitory postsynaptic potentials evoked by stimulation of the Schaffer collaterals. The onset and termination of this effect was in the order of minutes and no desensitization was observed. The selective 5-HT3 receptor antagonist, granisetron, when applied as a pretreatment completely prevented but did not reverse this action when given after administration of 2-methyl-5-HT while the non-specific 5-HT1,2 receptor antagonist, metergoline, was ineffective. These results suggest that the activation of 5-HT3 receptors reduces the efficacy of glutamatergic synaptic transmission in this area.
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