Effects of acute tyrosine/phenylalanine depletion on the selective processing of smoking-related cues and the relative value of cigarettes in smokers

Rationale: Acute tyrosine/phenylalanine depletion (ATPD) is a validated neurobiological challenge that results in reduced dopaminergic neurotransmission, allowing examination of the effects of a hypodopaminergic state on craving-related processes. Objectives: We studied 16 nonabstaining smokers (>10 cigarettes/day; 9 males; age 20-33 years) to whom was administered a tyrosine/phenylalanine-free mixture (TYR/PHE-free) and a balanced amino acid mixture (BAL) in a double-blind, counterbalanced, crossover design. Methods: Subjective cigarette craving, attentional bias to smoking-related word cues, relative value of cigarettes, negative mood, and expired carbon monoxide (CO) levels were measured at various timepoints through 300 min. Participants smoked at hourly intervals to prevent acute nicotine withdrawal during testing. Results: The TYR/PHE-free mixture, as compared to the BAL mixture, was associated with a greater increase in CO levels from baseline (p=0.01). Adjusting for the potential confounding influence of between-condition differences in CO levels across time, TYR/PHE-free mixture was associated with increased demand for cigarettes (p=0.01) and decreased attentional bias toward smoking-related words (p=0.003). There were no significant differences between conditions in either subjective craving or depressed or anxious mood (p values>0.05). Conclusion: Among nonabstaining daily smokers, acute dopaminergic depletion via ATPD may influence smoking behavior and indices of smoking-related motivation, such as attentional bias to smoking cues and relative cigarette value, which are not readily captured by subjective craving.