Reward Processing and Smoking

Tobacco addiction is a chronic brain disorder that is characterized by a negative affective state and craving for tobacco products upon smoking cessation, and relapse after a period of abstinence.1 However, we still do not fully understand the neurobiological mechanisms of why people smoke, and why they find it hard to quit. We do know that nicotine, particularly when consumed via cigarettes, is one of the most addictive drugs, and almost half the people who experiment with cigarettes become addicted to nicotine.2–4 Prolonged nicotine use leads to the development of dependence and compulsive smoking. Repeated administration of nicotine facilitates stimulus-response learning and sensitizes the response to nicotine, which plays a role in the transition for experimenting with cigarettes to habitual smoking.5,6 Smoking cues also lead to drug seeking and play a critical role in relapse.7 Recent evidence suggests that acute and protracted withdrawal symptoms lead to nicotine craving and contribute to relapse.1 During the last few decades, animal studies have greatly contributed to a better understanding of the neurobiology of nicotine addiction.8,9 The work of Markou and colleagues has provided important insight into the effects of nicotine withdrawal on mood states.10 The Markou laboratory has used the intracranial self-stimulation (ICSS) procedure to investigate the effects of nicotine withdrawal on mood.11 These studies have shown that acute nicotine administration increases the sensitivity to rewarding electrical stimuli.12,13 In contrast, cessation of nicotine administration leads to a decrease in sensitivity to rewarding electrical stimuli.10,12 This indicates that acute nicotine administration enhances reward function and that cessation of nicotine administration leads to a decrease in the reward value of nondrug reinforcers. The effect of nicotine withdrawal on cognition has not been as thoroughly investigated in animal models. However, there is evidence that nicotine withdrawal impairs cognitive function in rodents.14 There is a clear need for further fundamental research in both animal models and humans to better understand the mechanisms of tobacco use and dependence. The research presented in this issue provides new insights, with a particular focus on anhedonia and cognition. We know that nicotine induces mild euphoria and enhances cognitive function and these effects play a role in the initiation of smoking. People with psychiatric disorders are even more vulnerable to the addictive properties of cigarettes. They are more likely to progress to habitual smoking because nicotine counteracts specific impairments associated with their disorders.15,16 This is supported by research presented in this issue. Stone and colleagues show that during early adolescence children with high levels of anhedonia are more likely to start smoking than children with low levels of anhedonia.17 It is critical to prevent the onset of smoking and progression to compulsive smoking in this group of people as smoking greatly increases the risk for developing severe depression.1 Behavioral therapies and drug treatments that diminish anhedonia during early adolescence may decrease the number of young people that develop a tobacco addiction. There is also growing evidence from clinical studies that nicotine withdrawal impairs reward function and induces cognitive impairments that contribute to relapse. Anhedonia is often described as a decrease in the sensitivity to rewarding stimuli and plays an important role in the continuation of drug use.18 Several reports in this issue indicate that smoking cessation leads to impairments in brain reward function. The studies by Cook and colleagues used time-varying effect modeling to investigate the relationship between anhedonia and the level of nicotine dependence.19 These studies show that during the first week after smoking cessation anhedonia was more severe in people with a high level of dependence than in people with a low level of dependence. Hughes and colleagues developed a new survey that can be used to measure anticipated enjoyment from common rewards.20 The same survey was used to investigate the effect of smoking cessation on self-reported pleasure from rewards.21 As expected, after people quit smoking they reported a decrease in pleasure from common rewards. Oliver and colleagues used an electrophysiological method to investigate the effects of smoking cessation on brain reward function.22 They prepared test subjects with electroencephalogram (EEG) caps and analyzed the medial frontal negativity (MFN). The MFN signal allows the evaluation of expected and unexpected rewards on brain reward function. In this paradigm, unfair offers and withholding expected rewards leads to larger MFN amplitudes. Interestingly, people who switch to low nicotine cigarettes had a larger MFN amplitude after unpredicted no-reward trials. Changes in the MFN amplitude correlate with changes in firing of dopaminergic neurons in the ventral tegmental area.23 Therefore, this observation confirms that nicotine withdrawal is associated with an impairment in reward function. This observation is in line with another study that analyzed imaging data collected by the Human Connectome Project.24 This study reported that tobacco users display diminished right nucleus accumbens reactivity in response to rewards compared to nonsmokers. Therefore, these studies indicate that tobacco smoking leads to impairments in the reward system, which contributes to the continuation of tobacco use. In addition to affecting mood states, smoking cessation also has significant effects on cognitive function. There is extensive evidence that smoking enhances cognitive function and these effects are also observed in smokers who are not tobacco deprived.25 Therefore, the cognitive performance-enhancing effects of smoking are unlikely to be only due to withdrawal reversal. Smoking cessation also leads to severe cognitive impairments that may contribute to the continuation of smoking to prevent this aversive state.26 Several studies in this issue provide new insight into cognitive function in the continuation of smoking. The work by Maclean showed that during abstinence there is a negative correlation between craving and concerns about personal health.27 Thus, during tobacco withdrawal people are less concerned about their health and are therefore more likely to resume smoking. The delay discounting paradigm has also been used to study the development of tobacco addiction. There is evidence that smokers have a higher discounting rate (preferring a small reward immediately compared to a large reward later) for monetary gains compared to controls.28,29 Interestingly, work presented in this issue indicate that people with the largest increase in the discounting rate after smoking cessation are least likely to relapse.30 People received monetary rewards for each abstinence test and this may have contributed to the fact that people with the highest discounting rate were able to maintain abstinence. In line with these findings, Versace and colleagues emphasize the need to consider individual differences in reward sensitivity to identify smokers at higher risk of relapse and assign them to tailored interventions.31 Overall, these new studies suggest that smoking cessation leads to anhedonia, which has been shown to contribute to relapse. Smoking cessation also leads to cognitive changes that could affect the risk for relapse to smoking. These clinical studies provide critical insight into the mechanisms that contribute to relapse to smoking. A better understand of the factors that contribute to relapse is needed to develop new and more effective smoking cessation treatments. AWB was supported in part by National Institutes of Health grants DA039349 and DA042530 when working on this editorial.