Clinical meaning
Ethanol produces its effects through multiple neurotransmitter systems. Acutely, ethanol enhances GABA-A receptor function (the primary inhibitory neurotransmitter), causing sedation, anxiolysis, and motor impairment. It simultaneously inhibits NMDA glutamate receptors (the primary excitatory neurotransmitter), reducing excitatory neurotransmission. This dual mechanism (enhanced inhibition + reduced excitation) produces dose-dependent CNS depression. Ethanol also stimulates dopamine release in the nucleus accumbens (reward pathway) via disinhibition of VTA dopaminergic neurons and direct effects on opioid receptors, producing euphoria and reinforcing drinking behavior. Chronic alcohol exposure causes neuroadaptation: GABA-A receptors are downregulated (tolerance to sedation), and NMDA receptors are upregulated (compensatory excitatory tone). When alcohol is abruptly discontinued, this adapted state results in a relative excitatory excess: anxiety, tremor, autonomic hyperactivity, seizures, and potentially delirium tremens. Alcohol is metabolized primarily by hepatic alcohol dehydrogenase (ADH) to acetaldehyde, then by aldehyde dehydrogenase (ALDH) to acetate. Acetaldehyde is toxic and contributes to hangover symptoms and hepatotoxicity. Genetic polymorphisms in ADH and ALDH affect metabolism rate: East Asian populations commonly have ALDH2*2 variant (inactive ALDH) causing acetaldehyde accumulation and flushing reaction, which is protective against AUD. Chronic alcohol...