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

Abstract

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 anticonvulsant. 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 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 bidirectional actions on adenosine signalling: depressant concentrations of ethanol (50 mM) increased the basal extracellular concentration of adenosine under baseline conditions, leading to the inhibition of synaptic transmission, but it inhibited adenosine release during evoked seizure activity in brain slices. The reduction in activity-dependent adenosine release was in part produced by effects on NMDA receptors, although other mechanisms also appeared to be involved. Low concentrations of ethanol (10-15 mM) enhanced 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 been reported.

• Authors: Victoria Hughes, Magnus J E Richardson, Mark J Wall
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 175 Issue 9 Pg. 1471-1485 (05 2018) ISSN: 1476-5381 [Electronic] England
• PMID: 29361192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Chemical References

• Ethanol
• Adenosine

Topics

• Adenosine (metabolism, physiology)
• Animals
• Biosensing Techniques (methods)
• Dose-Response Relationship, Drug
• Ethanol (pharmacology)
• Excitatory Postsynaptic Potentials (physiology)
• Hippocampus (drug effects, metabolism, physiology)
• Male
• Rats
• Seizures (physiopathology)