Liver Tryptophan Pyrrolase, Brain 5-Hydroxytryptamine and Alcohol Preference

Abstract

There is considerable evidence suggesting that a deficiency in the cerebral indolylamine 5-HT (5-hydroxytryptamine or serotonin) may be a key factor in predisposition to alcohol (ethanol) consumption in both man and experimental animals (for a review, see Naranjo et al.,1986). Because of obvious methodological limitations, a central 5-HT deficiency in human alcoholism has not been demonstrated directly, but is inferred through indirect evidence, e.g. decreased availability of circulating tryptophan to the brain (Branchey et al., 1984) and decreased ratios in the urine of the concentration of the major 5-HT metabolite 5-HIAA (5-hydroxyindol-3-ylacetic acid) to that of the metabolites representative of other tryptophan-degradative pathways (namely indol-3-ylacetic acid for the tryptamine pathway and anthranilic acid for the hepatic kynurenine-nicotinic acid pathway) (Thomson & McMillen, 1987) in abstinent chronic alcoholics, and the ability of selective 5-HT uptake blockers to lower the extent of alcohol consumption by non-abstinent alcoholics (Naranjo et al., 1986, 1987). In addition to the ability of these 5-HT uptake blockers and of other modulators of central 5-HT metabolism and/or function to influence ethanol consumption in experimental animals (for references, see Naranjo et al., 1986), there is direct evidence for a central 5-HT deficiency in alcohol-preferring, but not in -non-preferring, strains of mice (Serri & Ely, 1984; Yoshimoto & Komura, 1987) and rats (Murphy et al., 1986, 1987), though with one exception (Korpi et al., 1988).