The Effect of Tryptophan Depletion on Alcohol Self‐Administration in Non‐Treatment‐Seeking Alcoholic Individuals

Abstract

Background Alcohol self‐administration in the laboratory has been used to evaluate pharmacological treatments and neurobiological mechanisms that underlie alcohol use in alcohol‐dependent individuals. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the amount of alcohol consumed in a self‐administration paradigm in non‐treatment‐seeking individuals with alcohol use disorders.Methods Individuals with alcohol dependence (n= 8) and alcohol abuse (n= 4) who were not seeking treatment were recruited by advertisement and participated in two test days, 1 week apart. Each test session was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double‐blind fashion. The test session began with a cue exposure session where subjects were exposed to their favorite alcoholic beverage and asked to rate their craving for alcohol. After this, subjects were administered a priming drink designed to raise blood alcohol levels to 0.02 g%. Subjects then had the opportunity to drink up to eight additional drinks, each designed to raise blood alcohol levels by 0.02 g%, or to receive $3 for each drink not consumed over a 2‐hr period.Results There were no significant differences in alcohol consumed or subjective intoxication with active tryptophan depletion compared with placebo. Self‐reported craving correlated with the amount of alcohol consumed in the session.Conclusions These data question the dependence of alcohol self‐administration on the ongoing synthesis of serotonin.