The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals.
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.
Petrakis
Ismene L
IL
Department of Psychiatry, Yale University, New Haven, Connecticut, USA. ismene.petrakis@yale.edu
Buonopane
Alessandra
A
O'Malley
Stephanie
S
Cermik
Omer
O
Trevisan
Louis
L
Boutros
Nashaat N
NN
Limoncelli
Diana
D
Krystal
John H
JH
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000097:blood / Q000378:metabolism* / Q000523:psychology; D000434:Alcoholic Beverages; D000437:Alcoholism / Q000097:blood / Q000378:metabolism* / Q000523:psychology; D000704:Analysis of Variance; D016739:Behavior, Addictive / Q000097:blood / Q000378:metabolism / Q000523:psychology; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D012646:Self Administration; D014364:Tryptophan / Q000172:deficiency*
D000431:Ethanol; D014364:Tryptophan