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

Eur J Pharmacol. 1992 Nov 24;224(1):51-6. doi: 10.1016/0014-2999(92)94817-f.


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 microM), exacerbated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5-HT3 receptor antagonist, Y-25130 (0.1-100 microM), or the 5-HT2 receptor antagonist, ketanserin (10, 100 microM), 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 microM) was about 20 times greater than that in the ketanserin-treated group (EC50, 33 microM). 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.

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Animals
  • Brain Ischemia / physiopathology*
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Hippocampus / drug effects*
  • Hippocampus / physiopathology
  • Hypoglycemia / physiopathology
  • Hypoxia / physiopathology
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Membrane Potentials / drug effects
  • Oxazines / pharmacology
  • Rats
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin Antagonists* / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*


  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Oxazines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • azasetron
  • 2-methyl-5-HT
  • Ketanserin