Evidence for prolonged recovery of dopaminergic transmission after detoxification in alcoholics with poor treatment outcome

It has been hypothesized that dysfunction of dopaminergic neurotransmission is involved in the pathogenesis of alcohol addiction. Therefore, peripheral dopamine levels, sensitivity of central dopamine receptors (apomorphine-induced Growth Hormone (GH) secretion), and the inhibitory efficacy of G-proteins on adenylyl cyclase activity (as an indicator for dopamine D2-receptor coupled second messenger mechanisms) were measured in 45 alcohol-dependent patients before and after detoxification and in 10 healthy controls. The time needed to adjust to abstinence conditions differed between patients with good and poor treatment outcome. In subsequent abstainers, effects of alcohol withdrawal were already found during the first 24 hours of abstinence (normalisation of GH response, increases in dopamine levels and the inhibitory efficacy of G-proteins). During the next 7 days of abstinence, no more significant changes were observed in the assessed variables. In subsequent relapsers, no significant effect of acute ethanol withdrawal on the same measures was found. However, at day 8 of abstinence, increases in apomorphine-induced GH secretion (towards normalisation), in dopamine plasma levels, and in the inhibitory efficacy of G-proteins (towards above-normal levels) were observed. This retarded adjustment of dopaminergic signal transduction seems to reflect the relapse risk of treatment nonresponders.