The role of dopamine in alcohol self-administration in humans: individual differences.

ABSTRACT

OBJECTIVE: To clarify dopamine's role in alcohol self-administration in a heterogeneous sample of drinkers using acute phenylalanine/tyrosine depletion (APTD). METHODS: Sixteen men with variable drinking histories were characterized on their ethanol-induced cardiac response, a marker previously proposed to index dopamine system reactivity and vulnerability to alcohol abuse. During separate sessions participants were administered (i) a nutritionally balanced (BAL) amino acid (AA) mixture, (ii) a mixture lacking the dopamine precursors, phenylalanine and tyrosine, and (iii) APTD followed by the dopamine precursor, L-DOPA. Five hours after AA administration, participants could earn units of alcohol using a progressive ratio breakpoint task. RESULTS: Alcohol self-administration was reduced in the APTD and APTD+L-DOPA conditions relative to the BAL condition. In both cases the changes were predicted by ethanol-induced cardiac change. CONCLUSIONS: The motivation to drink is likely regulated by more than one neurobiological mechanism. Individual differences in cardiac responsivity to ethanol might provide a peripheral marker of responsiveness to pharmacological manipulations of dopamine.