Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9425392 | Neuroscience | 2005 | 9 Pages |
Abstract
To determine potential mechanisms contributing to ethanol-induced cognitive impairment, we examined acute effects of ethanol on hippocampal N-methyl-d-aspartate receptors and forms of synaptic plasticity thought to underlie memory processing. In the CA1 region of rat hippocampal slices, ethanol partially inhibited N-methyl-d-aspartate receptor-mediated synaptic responses at concentrations up to 180mM. The block of synaptic N-methyl-d-aspartate receptors by 60mM ethanol occluded the effects of 10μM ifenprodil, an agent that has relative selectivity for N-methyl-d-aspartate receptors expressing NR1 and NR2B subunits. Ethanol did not occlude the effects of a low concentration of 2-amino-5-phosphonovalerate, an antagonist with less N-methyl-d-aspartate receptor subtype selectivity. Recent studies indicate that ifenprodil and other NR2B-selective antagonists inhibit N-methyl-d-aspartate receptor-dependent long-term depression but not long-term potentiation. We found that ethanol reversibly inhibited long-term depression in a manner consistent with its effects on synaptic N-methyl-d-aspartate receptors. Ethanol also inhibited the induction of N-methyl-d-aspartate receptor-dependent long-term potentiation, but the actions on long-term potentiation were complex and largely irreversible over the time course of our experiments. Furthermore, ethanol inhibited a form of long-term potentiation induced by very high frequency stimulation that does not depend on N-methyl-d-aspartate receptor activation. The effects of ethanol on both forms of long-term potentiation, but not on long-term depression, were at least partially reversed by block of GABA type A receptors with picrotoxin. These results indicate that pharmacologically relevant concentrations of ethanol exert preferential effects on a subtype of synaptic N-methyl-d-aspartate receptors in the CA1 hippocampal region. Inhibition of synaptic N-methyl-d-aspartate receptors appears to contribute strongly to ethanol-mediated long-term depression inhibition, but effects on long-term potentiation are complex, involving, at least partially, changes in GABAergic transmission.
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Authors
Y. Izumi, K. Nagashima, K. Murayama, C.F. Zorumski,