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


  • April 9, 2002.

  • Supported, in part, by Grants RO1-AA10107 (IP), KO2 AA 00261(JK), I-P50AA–12870 (JK), and K02-AA00171 (SO) from NIAAA, and by the Department of Veterans Affairs Alcohol Research Center.

Reprint requests: Ismene Petrakis, MD, West Haven Veterans Administration Medical Center 116-A, 950 Campbell Avenue, West Haven, CT 06516; Fax: 203–937–4791; E-mail:


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.