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


OBJECTIVE
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).


CONCLUSIONS
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.
Hitsman
Brian
B
Centers for Behavioral and Preventive Medicine, The Miriam Hospital and Brown Medical School, Coro Building, Suite 500, 1 Hoppin Street, Providence, RI 02903, USA. brian_hitsman@brown.edu
MacKillop
James
J
Lingford-Hughes
Anne
A
Williams
Tim M
TM
Ahmad
Faheem
F
Adams
Sally
S
Nutt
David J
DJ
Munafò
Marcus R
MR
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D018592:Cross-Over Studies; D003463:Cues; D004298:Dopamine / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D010649:Phenylalanine / Q000172:deficiency*; D011930:Reaction Time; D012907:Smoking / Q000523:psychology*; D016540:Smoking Cessation / Q000523:psychology; D014443:Tyrosine / Q000172:deficiency*
D000596:Amino Acids; D014443:Tyrosine; D010649:Phenylalanine; D004298:Dopamine