Neuroprotective effect of 5-HT₃ receptor antagonist on ischemia-induced decrease in CA1 field potential in rat hippocampal slices

The effect of 5-HT₃ receptor agonists and antagonists on the hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 field potential elicited by stimulation of Schaffer collaterals was investigated using rat hippocampal slices. Treatment with the 5-HT₃ receptor agonist, 2-methyl-5-HT (1-10 μM), exaceebated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5-HT₃ receptor antagonist. Y-25130 (0.1-100 μM), or the 5-HT₂ receptor antagonist, ketanserin (10, 100 μM), produced dose-dependent neuroprotection against the ischemia-induced decrease. However, in normal non-ischemic solution these treatments did not significantly change the CA1 field potential. The protective action of Y-25130 was blocked by co-treatment with 2-methyl-5-HT. The magnitude of protection in the Y-25130-treated group (EC₅₀, 1.8 μM) was about 20 times greater than that in the ketanserin-treated group (EC₅₀, 33 μM). The present study demonstrated that stimulation of 5-HT₃ receptors plays a detrimental role in the development of ischemic damage, whereas blockade of the 5-HT₃ receptor plays a neuroprotective role in ischemic damage, suggesting a facilitatory role of 5-HT neurons in ischemia-induced neuronal deficits.