The mechanisms underlying the behavioral effects of alcohol have not been established. This project studied the cellular and molecular actions of ethanol on neurotransmitter-activated membrane ion channels in mammalian neurons using the whole-cell patch-clamp recording technique. The ion current activated by the glutamate agonist NMDA was inhibited by ethanol; the inhibition increased in a concentration-dependent manner over the concentration range 5 - 50 mm, a range that produces intoxication. This concentration range had relatively little effect on the ion currents activated by the glutamate agonists kainate and quisqualate; however, these currents were significantly inhibited by ethanol in a concentration-dependent manner over the concentration range 50 - 100 mm, a range that produces general anesthesia. Similar effects of ethanol were observed on NMDA and non-NMDA glutamate receptor-mediated excitatory postsynaptic potentials (EPSPs). The potency for inhibition of the NMDA-activated current by several alcohols was linearly related to their intoxicating potency, suggesting that the alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication. GABA-A activated ion current was potentiated by ethanol in some neurons and not affected by ethanol in other neurons. The concentration range that potentiated GABA-A activated current was 10-50 mM. GABA-A activated current was also potentiated by benzodiazepines, suggesting that the augmentation of this current by ethanol may contribute to the anxiolytic actions of ethanol. Intoxicating concentrations of ethanol were also found to potentiate the ion current mediated by activation of the 5-HT-3 type of serotonin receptor. Behavioral experiments suggest that this effect may be associated with the recognition of ethanol action. The preceding observations are consistent with the idea that the behavioral effects of ethanol may result from actions of ethanol on these receptor-gated ion channels.
