Altered conversion of tryptophan to kynurenine in newly abstinent alcoholics

Badawy et al. (1973, 1975, 1979, 198Oa, 198Ob) have shown in many reports that chronic alcohol ingestion by rats results in higher central nervous system (CNS) levels of tryptophan (Trp) and serotonin (WIT). They argue that this occurs because chronic ethanol intake inhibits synthesis of hepatic tryptophan oxygenase (TPO), the major quantitative catabolic enzyme for Trp metabolism (Young et al. 1978). Extrapolating from rats to humans, such a biochemical process suggests that drinking behavior might be reinforced by the higher brain Trp and 5-HT concentrations resulting from ethanol-induced suppression of TPO. Though data on this matter are confusing and inconsistent, it has been shown in the rat that higher brain concen~ations of Trp and 5-HT, resulting from inhibition of hepatic TPO, are associated with altered CNS function (Litman and Correia 1985). Finally, the report that zimelidine reduced drinking behavior among recently detoxified alcoholics (Naranjo et al. 1984) is not only consistent with a role for 5-