Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans

Abstract

Preclinical research documents that, aside from the primary and secondary reinforcing effects of nicotine intake itself, nicotine also acutely enhances the reinforcing efficacy of non-drug reinforcers ("rewards"). Study of these effects in humans has largely been overlooked, but very recent findings suggest they may have clinical implications for more fully understanding the persistence of tobacco dependence. This overview first outlines the topic and notes some recent human studies indirectly addressing nicotine effects on related responses (e.g., subjective ratings), explaining why those findings do not directly confirm enhancement of behavioral reinforcement per se due to nicotine. Then, the methodology used in the subsequently presented studies is described, demonstrating how those studies specifically did demonstrate enhancement of reinforced responding for non-drug rewards. The main section focuses on the limited controlled research to date directly assessing nicotine's acute reinforcement-enhancing effects in humans, particularly as it relates to reinforced behavioral responding for non-drug rewards in non-human animal models. After detailing those few existing human studies, we address potential consequences of these effects for dependence and tobacco cessation efforts and then suggest directions for future research. This research indicates that nicotine per se increases responding in humans that is reinforced by some rewards (auditory stimuli via music, visual stimuli via video), but perhaps not by others (e.g., money). These reinforcement-enhancing effects in smokers are not due to dependence or withdrawal relief and can be restored by a small amount of nicotine (similar to a smoking lapse), including from e-cigarettes, a non-tobacco nicotine product. Future clinical research should examine factors determining which types of rewards are (or are not) enhanced by nicotine, consequences of the loss of these nicotine effects after quitting smoking, potential individual differences in these effects, and the possibility that nicotine via nicotine replacement therapy and non-nicotine quit medications may attenuate loss of these effects upon quitting. Further study with humans of nicotine's reinforcement-enhancing effects may provide a more complete understanding of smoking persistence and added mechanisms of cessation medication efficacy.

Vicarious trial-and-error is enhanced during deliberation in human virtual navigation in a translational neuroeconomic task

“…The trend for smokers may have been driven by a tendency for smokers to report higher subjective enjoyment in the Movie Row task (in the post-video star ratings), and thus may have been more willing to wait for videos because they found them more rewarding. Such a result seems consistent with other work demonstrating that, at least for acute administration, nicotine can enhance the rewarding effects of some non-drug rewards (music and video stimuli, but not money, Perkins, Karelitz, & Boldry, 2017).…”

Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine

“…These data suggest that nicotine's role as a reinforcement enhancer may be more significant for males. 6,8 In other words, nicotine enhances the rewarding effects that drove initial chamber preference in male mice, such that stress reinstates CPP only to the initially preferred chamber.…”

“…Nicotine, the primary psychoactive component in tobacco, is a relatively weak primary reinforcer . However, nicotine can also enhance the rewarding properties of nonpharmacological stimuli, enhance cognitive function, and interact with stress and anxiety to support addiction‐related behaviors. Interactions between these various effects of nicotine may account for the well‐documented interindividual variability in nicotine use and relapse observed in both human studies and rodent models .…”

Lasting reduction of nicotine‐seeking behavior by chronic N‐acetylcysteine during experimental cue‐exposure therapy

“…Thus, reintroduction of S D+ by signaling drug availability may favor the search of the substance, and the contingent CS + may subsequently have maintained drug‐seeking behavior . Moreover, nicotine acts not only as a primary reinforcer but also as a reinforcement enhancer, as demonstrated in both preclinical and clinical studies: this may explain the increased salience for nicotine‐related stimuli.…”