99 - Tryptophan Metabolism and Alcoholism

Abstract

This chapter reviews alcoholism and its effect on tryptophan metabolism. Acute and chronic ethanol intake and subsequent withdrawal exert major effects on tryptophan (Trp) metabolism and disposition in man and experimental animals. In rats, activity of the major Trp-degrading enzyme, liver Trp pyrrolase (TP) is enhanced by acute, but inhibited after chronic, ethanol administration, then enhanced during subsequent withdrawal. These changes lead to corresponding alterations in brain serotonin synthesis and turnover mediated by appropriate changes in circulating Trp availability to the brain. Brain serotonin is deficient in the alcohol-preferring C57BL/6J mouse strain and many alcohol-preferring rat lines. Acute ethanol intake also inhibits brain serotonin synthesis by the activating liver TP. This serotonin depletion may form the biological basis of alcohol-induced depression, aggression, and the loss of control in susceptible individuals. Chronic alcohol intake in dependent subjects may be associated with the liver TP inhibition and a consequent enhancement of brain serotonin function, whereas subsequent withdrawal may induce the opposite effects. There may be a role for the excitotoxic Trp metabolite quinolinate in the behavioral disturbances of the alcohol-withdrawal syndrome. Some abstinent alcoholics may have a central serotonin deficiency, which they correct by liver TP inhibition through drinking.