Dopamine and alcohol relapse: D-1 and D-2 antagonists increase relapse rates in animal studies and in clinical trials

A considerable number of animal studies on the effects of dopaminergic agen ts on alcohol intake behavior have been performed. Acute alcohol administra tion in rats induces dopamine release in the caudate nucleus and in the nuc leus accumbens, an effect related among others to reinforcement. It has bee n repeatedly suggested that D-1 and D-2 receptor activation mediates reward . As alcohol consumption and dopaminergic transmission seem to have a close relationship, all kinds of dopaminergic agents may be regarded as putative therapeutics for preventing relapse. In a prospective European double-blin d multicenter clinical trial, comparing the D-1, D-2, D-3 antagonist flupen thixol and placebo in 281 chronic alcohol-dependent patients (27.4% women), the application of the Lesch typology made an outcome differentiation poss ible, it could be shown in which patients flupenthixol administration was f ollowed by a significantly higher relapse rate and in which patient groups no differences were found when compared to placebo. Copyright (C) 2001 Nati onal Science council, ROC and S. Karger AG, Basel.