22.03 Mechanism of Alcohol Action

Ethanol influences many sites in the central nervous system, including 5-HT and glycine receptors, and G protein-coupled inwardly rectifying K⁺ (GIRK) channels. However it appears its major sites of action at low to moderate doses are GABA_A receptors, and NMDA receptors at higher doses. At GABA_A receptors it enhanceS GABA activation, by increasing the mean ion channel open time and facilitating GABA binding. At NMDA receptors it appears to act as a non-competitive inhibitor. Thus ethanol can reduce excitation and increase inhibition in the brain, leading to over-inhibition.

Although GABA_A receptors are ubiquitously (widely) distributed throughout the CNS, the location of GABA_A receptors modulated by ethanol is significant. Receptors in the cerebellum likely contribute to the impaired motor coordination and ataxia induced by ethanol. Receptors in specific thalamic nuclei may mediate some sedative, hypnotic and anaesthetic effects, while those in the hippocampus, amygdala and neocortical regions contribute to the cognitive impairment, anxiolysis and amnesia.