A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence

Abstract

Background: Tobacco smoking, driven by the addictive properties of nicotine, is the most prevalent preventable cause of death in the Western world. Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment.

Methods: To test this hypothesis, we conducted a randomized, double-blind, placebo-controlled, crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers. A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward.

Results: Despite expected adverse effects such as nausea, nicotine significantly increased response bias toward the more frequently rewarded condition, at the expense of accuracy, independent of effects on attention or overall vigilance. Additionally, response bias on placebo was greater in participants who received nicotine in the first session, indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week.

Conclusions: These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects. This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence.

Trial registration: ClinicalTrials.gov NCT00383747.

Figures

Figure 1. Response Bias

Nicotine treatment increased response bias in the signal detection task (main effect of Treatment: F1, 28=8.18, p=0.008) indicating increased responding for the more rewarded (rich) Stimulus Type. Data are presented as means ± standard error.

Figure 2. Response Bias at Visit One and Visit Two

Nicotine significantly increased response bias at both visits (main effect of Treatment at visit 1: F1, 28=4.31, p=0.047; visit 2: F1, 28=4.76, p=0.038).

Figure 3. Accuracy

A main effect of Stimulus Type (F1,28=36.07, p=<0.0001) indicates greater accuracy for the more rewarded (rich) stimulus. A Treatment by Stimulus Type interaction (F1,28=5.08, p=0.03) indicated that, compared to placebo, nicotine was associated with greater accuracy for the rich stimulus but lower accuracy for the lean stimulus.

Figure 4. Reaction Time

A significant main effect of both Stimulus Type (F1,28=36.6, p=1.6E−6) and Treatment (F1,28=4.75, p=0.04) indicated that RT was faster for the more rewarded (rich) stimulus and in the nicotine condition vs placebo.