Regional effects of ethanol on glutamate levels, uptake and release in slice and synaptosome preparations from rat brain.

Abstract

Chronic ethanol treatment effects a decrease in K+-stimulated endogenous glutamate release and an increase in glutamate levels in rat frontal cortex. This treatment also increases (3H)-glutamate uptake in striatal and hippocampal slices. No uptake changes were observed in either cortical slices or synaptosomes. Ethanol withdrawal increases K+-stimulated glutamate release in cortex and hippocampus and glutamate levels in cortex, striatum and hippocampus. (3H)-glutamate uptake is increased in striatum of withdrawn animals. Thus, regional variations were observed with regard to both effect and degree of effect. Because in vitro and acute ethanol treatments had no effect on uptake or release, these changes probably result from activated feedback mechanisms that attempt to compensate for ethanol's action on brain systems rather than direct effects on membrane structure. Combined level-release data suggest an effect of ethanol on glutamate distribution in cortex and striatum. Combined uptake and release data indicate a correlation between diminished glutamate synaptic activity and the addicted state, and between heightened glutamate synaptic activity and the withdrawn state.