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.
RCT Entities:
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.
Authors: Martin H Plawecki; Leah Wetherill; Victor Vitvitskiy; Ann Kosobud; Ulrich S Zimmermann; Howard J Edenberg; Sean O'Connor Journal: Alcohol Clin Exp Res Date: 2012-07-20 Impact factor: 3.455
Authors: Ismene L Petrakis; Stephanie O'Malley; Bruce Rounsaville; James Poling; Colette McHugh-Strong; John H Krystal Journal: Psychopharmacology (Berl) Date: 2003-11-21 Impact factor: 4.530
Authors: Amira Pierucci-Lagha; Richard Feinn; Vania Modesto-Lowe; Robert Swift; Maggie Nellissery; Jonathan Covault; Henry R Kranzler Journal: Psychopharmacology (Berl) Date: 2003-09-10 Impact factor: 4.530
Authors: Ulrich S Zimmermann; Inge Mick; Manfred Laucht; Victor Vitvitskiy; Martin H Plawecki; Karl F Mann; Sean O'Connor Journal: Psychopharmacology (Berl) Date: 2008-10-21 Impact factor: 4.530
Authors: Shosuke Suzuki; Maggie Mae Mell; Stephanie S O'Malley; John H Krystal; Alan Anticevic; Hedy Kober Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2019-12-28