Effects of ethanol on neurotransmitter release by rat brain cortical.

Using a double label technique to preload rat brain cortex slices with different radioactive neurotransmitters (or precursor choline), we have studied the effects of ethanol on the electrically stimulated release of these transmitters. Ethanol inhibited the release of these transmitters, acetylcholine being the most sensitive and occurring at concentrations compatible with moderate to severe intoxication in the rat (IC50 equals 0.17 M). The order of sensitivity to ethanol was acetylcholine greater than serotonin greater than dopamine greater than norepinephrine greater than glutamate greater gamma-aminobutyric acid. Two higher alcohols and two barbiturates were also shown to have a greater inhibitory effect on the stimulated release of acetylcholine than of norepinephrine. The concentrations of all the drugs tested required for 50% inhibition of release of acetylcholine and norepinephrine correlated well with their lipid solubility when corrected for their molecular volumes. The effect of tetrodotoxin and of ouabain on neurotransmitter release was also studied. A comparison of the effects of these two drugs with those of ethanol suggests that the effect of ethanol is consistent with an inhibition of the action potential by this drug, although a specific effect of ethanol on the excitation-coupling process at the synapse cannot by discarded.