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Chapter 8. Neurobiology of Alcohol

Clifford M. Knapp, Ph.D.; Domenic A. Ciraulo, M.D.; Henry R. Kranzler, M.D.
DOI: 10.1176/appi.books.9781585623440.345885

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Excerpt

Ethanol is a small molecule that readily distributes into highly perfused tissues such as the brain. Peak levels of ethanol are attained approximately 30 minutes after ingestion of an alcoholic drink. A single drink of ethanol produces a biphasic effect with a rapid stimulatory phase associated with an increase in blood ethanol concentrations followed by a depressant phase as the blood concentration diminishes. Although the ethanol from a single drink is readily metabolized in two steps involving the enzymes alcohol dehydrogenase and aldehyde dehydrogenase, this process follows zero-order kinetics. Accordingly, there is a decrease in the percentage of ethanol metabolized per given unit of time, as the dose of this agent is increased.

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Table Reference Number

The antianxiety, motor-impairing, and sedative-hypnotic effects of ethanol may be produced by the activation of -aminobutyric (GABA)A receptors.

Ethanol may interact with GABAA receptors by enhancing GABA release, increasing brain neurosteroid levels, and/or by directly acting on GABAA receptors that contain 4 or 6 subunits.

Decreased GABAA receptor sensitivity and N-methyl-d-aspartate (NMDA) receptor up-regulation may play important roles in the development of physical dependence on ethanol.

Ethanol-induced dopamine release within the nucleus accumbens may produce the reinforcing effects of alcohol.

Cannabinoid CB1, nicotinic, opioid, and serotonin 5-HT3 receptors may alter the reinforcing effects of ethanol by facilitating dopamine release.

Endogenous opioid peptides, including the enkephalins, may promote ethanol consumption while other peptides, such as neuropeptide Y, may have inhibitory effects on alcohol-seeking behaviors.

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Which of the following statements concerning alcohol metabolism is true?
2.
Lower levels in the caudate, putamen, and ventral striation of which of the following dopamine receptors has been associated with early-onset alcohol dependence?
3.
Blocking of which of the following serotonin (5-HT) receptors may reduce ethanol consumption by individuals with early-onset alcoholism?
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