NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat

Abstract

The effect of ethanol (EtOH) on synaptic transmission mediated by N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors was investigated in slices from adult rat hippocampus. Synaptic responses were elicited by stimulation of stratum radiatum and were recorded in CA1 stratum radiatum or stratum pyramidale. Population EPSPs (pEPSPs) mediated by NMDA receptor activation were isolated by application of a solution containing the kainate/quisqualate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione and either low (0.1 mM) Mg2+ or 100 microM bicuculline. Increasing concentrations of EtOH produced increasing inhibition of NMDA receptor-mediated pEPSPs with EtOH concentrations between 1 and 50 mM. At a concentration of 50 mM, EtOH inhibited NMDA receptor-mediated pEPSPS by 43%; the inhibition by 100 mM EtOH was not significantly different from that produced by 50 mM. Methanol and 1-butanol also inhibited the NMDA receptor-mediated pEPSPs; the potency of the alcohols for inhibition of NMDA receptor-mediated pEPSPs was 1-butanol greater than ethanol greater than methanol. pEPSPs mediated by non-NMDA glutamate receptors were isolated by the application of the NMDA receptor antagonist d,1-2-amino-5-phosphonovaleric acid in the presence of 1.5 mM Mg2+. These pEPSPs were not significantly affected by 50 mM EtOH, whereas 100 mM EtOH reduced the amplitude of these pEPSPs by 9%. The observations indicate that synaptic excitation mediated by NMDA receptors in tissue from adult rat is inhibited by intoxicating concentrations of EtOH. The data are consistent with the hypothesis that EtOH-induced inhibition of EPSPs mediated NMDA receptors may contribute to the intoxicating effects of EtOH.

Ethanol Reduces Neuronal Excitability of Lateral Orbitofrontal Cortex Neurons Via a Glycine Receptor Dependent Mechanism

“…This finding is consistent with other reports showing that EtOH decreases the amplitude of NMDA EPSCs in various brain regions including the mPFC (Weitlauf and Woodward, 2008), hippocampus (Lovinger et al, 1990), amygdala (Roberto et al, 2004), BNST (Kash et al, 2008), and striatum (Wang et al, 2007). In the present study, 66 mM EtOH significantly inhibited NMDA EPSCs while lower EtOH concentrations (11, 33 mM) had little effect suggesting that NMDA receptors in the adult OFC, unlike some areas, are not particularly sensitive to EtOH.…”

Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway

“…However, studies showing the activation of MAP kinase by Ca 2+ via NMDA receptors or voltage-dependent Ca 2+ channels have been very well documented [33][34][35] . Since ethanol inhibits both voltage-gated Ca 2+ channels and NMDA receptor-associated Ca 2+ influx [36][37][38] , it is possible that a decrease in the Ca 2+ concentration in striatal neurons might decrease the phosphorylation of MAP kinase. Future studies will be required to identify the site and mechanism underlying the effects of ethanol on this pathway.…”

Translocation of Autophosphorylated Calcium/Calmodulin-dependent Protein Kinase II to the Postsynaptic Density

“…Translocation of CaMKII in Hippocampal Slices-Preparation and electrophysiological recordings from hippocampal slice were described previously (23). Four to six slices (400 m, 3-6 week old rats) were divided into control/experimental hemislices and maintained in oxygenated, artificial cerebrospinal fluid for 60 min at 32°C.…”