22.05 Long-Term Adaptive Changes with the use of Alcohol

Prolonged use of ethanol alters the balance of neuronal excitation and inhibition, and appears to cause adaptive changes in nervous system function. Chronic intermittent or heavy prolonged usage can lead to adaptive changes in the brain, including changes in GABA_A receptor expression and subunit reshuffling. Such changes in expression and subunit reshuffling substantially alter the pharmacological properties of GABA_A receptors, with important functional consequences.

Long-term use of ethanol may lead to tolerance, such that higher doses are required to produce the same effect, and dependence, manifesting as cravings for the substance, and a physical withdrawal syndrome. The dose required and period of usage to elicit dependence, however, may vary between individuals. The rewarding effects of ethanol may arise from its action at GABA_A receptors in the ventral tegmental area and nucleus accumbens of the dopamine mesolimbic “reward/motivational salience” pathway. Mood state also impacts upon dependence, and alcohol use disorders are more common in sufferers of anxiety and depression. There is also evidence of genetic susceptibility to alcohol dependence, and several candidate genes have been identified including genes encoding GABA receptors.

The alcohol withdrawal syndrome manifests as insomnia and sleep disturbances, anxiety, hyperexcitability, delirium tremens, hyperalgesia, and lowered seizure threshold (increased risk of seizures), and can be treated with benzodiazepines.