EVIDENCE FOR A SELECTIVE EFFECT OF ETHANOL ON N-METHYL-D-ASPARTATE RESPONSES - ETHANOL AFFECTS A SUBTYPE OF THE IFENPRODIL-SENSITIVE N-METHYL-D-ASPARTATE RECEPTORS

An extracellular electrophysiological approach was used to determine t he effect of ethanol on responses to N-methyl-D-aspartate (NMDA) acros s several brain regions in urethane-anesthetized rats. The results ind icated that, in most brain regions, ethanol inhibited the NMDA-induced increases in firing rate for some, but not all, spontaneously active neurons. Ethanol functioned as an NMDA antagonist for some neurons in the medial septum, red nucleus, deep mesencephalic nucleus, substantia nigra reticulata, ventral tegmental area and cerebellum. In the hippo campus, ethanol inhibited NMDA responses from all neurons, However, et hanol was not found to be active against NMDA responses in the lateral septum, suggesting that there is a degree of regional specificity for ethanol inhibition of NMDA responses. It was then established in unan esthetized rats that ethanol also antagonized responses to NMDA in som e, but not ail, neurons in the medial septum and cortex, indicating th at the differential action of ethanol on NMDA responses obtained in th e urethane-anesthetized rats was not due to the anesthetic. Based on a n earlier study showing that the effects of ifenprodil and ethanol on NMDA responses were correlated, the ability of ethanol to inhibit NMDA responses was compared with changes produced by ifenprodil on the sam e neurons, where ethanol did or did not affect NMDA responses. In the several brain regions investigated,ethanol inhibited NMDA responses in a subgroup of neurons in which ifenprodil inhibited NMDA-induced incr eases in firing. For all neurons investigated, if a cell was insensiti ve to ifenprodil antagonism of NMDA responses then ethanol also was in effective against the response to NMDA. These results suggest that eth anol acts on an ifenprodil-sensitive NMDA receptor subtype. Given that previous investigations have suggested that the NMDA receptor type 2B subunit is essential for the action of ifenprodil, the positive relat ionship between the actions of ifenprodil and ethanol on responses to NMDA is consistent with the hypothesis that the combination of specifi c receptor subunits forming an NMDA receptor on a neuron determines th e ability of ethanol to antagonize an NMDA response.