3 years ago

Acute ethanol exposure has bidirectional actions on the endogenous neuromodulator adenosine in rat hippocampus

Mark J Wall, Magnus J E Richardson, Victoria Hughes
Background and purpose Ethanol is a widely used recreational drug with complex effects on physiological and pathological brain function. In epileptic patients the use of ethanol can modify seizure initiation and subsequent seizure activity with reports of ethanol being both pro and anti-convulsant. One proposed target of ethanol's actions is the neuromodulator adenosine, which is released during epileptic seizures to feedback and inhibit the occurrence of subsequent seizures. Here we have investigated the actions of acute ethanol exposure on adenosine signalling in rat hippocampus. Experimental approach We have combined electrophysiology with direct measurements of extracellular adenosine using microelectrode biosensors in rat hippocampal slices. Key results We found that ethanol has bi-directional actions on adenosine signalling: depressant concentrations of ethanol (50 mM) can increase the basal extracellular concentration of adenosine, leading to the inhibition of synaptic transmission, but it can also inhibit activity-dependent adenosine release during seizures. The reduction in activity-dependent adenosine release is in part produced by effects on NMDA receptors although other mechanisms also appear to be involved. Low concentrations of ethanol (10-15 mM) can enhance pathological network activity by selectively blocking activity-dependent adenosine release. Conclusions and implications The complex dose-dependent actions of ethanol on adenosine signalling could in part explain the mixture of pro-convulsant and anticonvulsant actions of ethanol that have previously both been reported.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bph.14152

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