Effects of sigma receptor agonists or antagonists on hypoxia/hypoglycemia-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collaterals were investigated using rat hippocampal slices. Treatment with sigma receptor antagonists such as haloperidol. NE-100 and rimcazole produced a concentration-dependent attenuation of the hypoxia/hypoglycemia-induced decrease in CA1 presynaptic fiber spikes. The order of potency of protection against hypoxia/hypoglycemia-induced reduction in CA1 presynaptic potential was: NE-100 = haloperidol > rimcazole. Treatment with sigma receptor agonist DTG potentiated the hypoxia/hypoglycemia-induced decrease in the CA1 presynaptic potential, whereas SKF10047 which possesses an affinity for phenycyclidine site attenuated the decrease of potential. NE-100 antagonized a functional deficit induced by DTG, but unaffected the improving effect induced by SKF10047. The present results suggest a facilitatory role of sigma receptor stimulation in hypoxia/hypoglycemia-induced an impairment of neurophysiological functions in CA1 presynaptic regions of hippocampal slices.
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