ETHANOL INHIBITION OF NMDA CURRENTS IN ACUTELY DISSOCIATED MEDIAL SEPTUM DIAGONAL BAND NEURONS FROM ETHANOL-DEPENDENT RATS

The effect of acutely applied ethanol and the impact of chronic ethano l treatment, sufficient to induce tolerance and physical dependence, o n N-methyl-D-aspartate (NMDA) receptor function were studied in acutel y isolated neurons from the medial septum/diagonal band (MS/DB) of adu lt rats using whole cell, patch-clamp electrophysiology. There was a s mall positive correlation for capacitance and current amplitude activa ted by 100 mu M NMDA for all groups. Also, cell membrane capacitance w as significantly smaller for Ethanol Dependent (similar to 80-84%) tha n either Naive or Control cells. Therefore NMDA-activated responses we re normalized for capacitance (current density, pA/pF) across all thre e groups. NMDA-activated (30-1000 mu M) responses were significantly l arger in cells from Control and Ethanol Dependent rats relative to tho se from Naives. In addition, estimated maximal responses were signific antly larger for Ethanol Dependent cells, compared to either Control o r Naive, respectively, while EC(50)s and slopes were not significantly different. Acute 60 mM ethanol significantly inhibited responses to 1 00 mu M NMDA in all three groups, however, mean ethanol inhibition was 12-25% smaller after ethanol dependence. There was no evidence of acu te tolerance to ethanol inhibition for any group, but examination of p atterns of inhibition for individual neurons showed a few cells were r esistant to ethanol or exhibited progressive loss of ethanol inhibitio n. These results suggest that NMDA receptor function in acutely isolat ed MS/DB neurons is increased following in vivo chronic ethanol treatm ent, and shows resistance to acute ethanol inhibition suggesting NMDA receptor-mediated cellular tolerance. (C) 1998 Elsevier Science B.V.