Effects of acute tryptophan depletion on the attentional salience of smoking cues

Rationale There is increasing evidence linking cigarette craving and smoking behavior to serotonergic neurotransmission. Objectives The purpose of the current study was to examine the effects of a serotonergic challenge on the attentional salience of various cues associated with cigarettes. We hypothesized that cigarette-related word cues would be more distracting after acute tryptophan depletion than after a placebo challenge. We also hypothesized that smokers vulnerable to recurrent depression would show greater attentional bias towards these cues than smokers without a history of depression. Methods Thirty-four smokers diagnosed as having (n=15) or lacking (n=19) a history of DSM-IV major depressive disorder (MDD) underwent acute tryptophan depletion (ATD) and placebo challenges in double-blind and counterbalanced order 1 week apart. Five hours after consumption of each mixture, subjects completed a modified Stroop task to measure attentional bias to smoking-related, positive affect, and negative affect word cues. Stroop interference was calculated as a difference score between latencies for the motivationally salient and the neutral(furniture) word lists. Results Controlling for change in dysphoric mood from baseline to 5 h, repeated measures MANOVAs showed that ATD, as compared to placebo challenge, produced greater interference for smoking word cues [F(1,29)=4.15, p=0.05], but not for negative [F(1,29)=2.78, p=0.11] or positive [F(1,29)=1.60, p=0.22] affect word cues. Conclusions Acutely compromising central serotonergic neurotransmission via ATD heightens the attentional salience of cigarette-related cues, perhaps by triggering reward and motivational deficits underlying nicotine dependence.