CROCIN ANTAGONIZES ETHANOL INHIBITION OF NMDA RECEPTOR-MEDIATED RESPONSES IN RAT HIPPOCAMPAL-NEURONS

We have previously found that crocin (crocetin di-gentiobiose ester) a ntagonizes the inhibitory effect of ethanol on long-term potentiation in the rat hippocampus in vivo and in vitro. To explore mechanisms und erlying the antagonism of crocin against ethanol, we investigated the effects of ethanol and crocin on synaptic potentials mediated by N-met hyl-D-aspartate (NMDA) receptors in the dentate gyrus of rat hippocamp al slices. Synaptic potential mediated by non-NMDA receptors was recor ded in normal medium (1.3 mM Mg2+), while NMDA receptor-mediated synap tic potential was isolated in low (0.13 mM) Mg2+ medium containing the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M). Crocin (10 mu M) alone did not affect synaptic potentials medi ated by non-NMDA nor NMDA receptors. Non-NMDA response was slightly in hibited by 100 mM ethanol, while NMDA response was selectively inhibit ed by lower concentrations (10-50 mM) of ethanol. Crocin (10 mu M) did not affect the inhibition of non-NMDA response by 100 mM ethanol, but significantly blocked the inhibition of NMDA response by 10-50 mM eth anol. In addition, we performed whole-cell patch recording with primar y cultured rat hippocampal neurons, and confirmed that crocin blocked ethanol inhibition of inward currents evoked by application of NMDA. T hese results suggest that crocin specifically antagonizes the inhibito ry effect of ethanol on NMDA receptor-mediated responses in hippocampa l neurons. (C) 1998 Elsevier Science B.V.