Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers
Introduction
Dysfunctional reward processing, which commonly manifests as the overvaluation of drug-related rewards and undervaluation of other non-drug reinforcers (e.g., food, sex, money), plays a key role in substance abuse (Blum et al., 2000, Garavan et al., 2000, Goldstein et al., 2007, Kalivas and Goldstein, 2005, Versace et al., 2012). This is true for nicotine-dependent individuals, who demonstrate reduced reward reactivity to non-drug reinforcers during nicotine withdrawal (Al-Adawi and Powell, 1997, Powell et al., 2002a, Powell et al., 2002b, Powell et al., 2004). Conversely, when present, nicotine enhances the reward value of non-drug stimuli leading tobacco smokers to experience relatively heightened pleasure or potentiated reward responsiveness (Barr et al., 2008, Dawkins et al., 2006, Kenny and Markou, 2006).
Nicotine's ability to enhance reward function suggests that the propensity to smoke may be higher in those with blunted hedonic capacity (Audrain-McGovern et al., 2012), implying that nicotine may ameliorate an underlying disruption in reward function (Cardenas et al., 2002, Janes et al., 2015). This hypothesis would explain the high prevalence of nicotine dependence in psychiatric disorders that are characterized by blunted hedonic capacity such as major depressive disorder (Glassman et al., 1990) and schizophrenia (de Leon et al., 1995, de Leon and Diaz, 2005). Such a hypothesis may extend to a more general population without clinically significant anhedonia, suggesting that individuals with sub-clinical disruption in reward function may have increased motivation to smoke.
Although reduced reward function is thought to play a role in maintaining nicotine dependence (Bühler et al., 2010, Koob and Le Moal, 2001, Volkow et al., 2010), it is still unclear if blunted reward processing is directly linked to an increased desire to smoke. Preliminary support for this notion comes from evidence showing that anhedonia – a blunting of hedonic capacity – is associated with greater nicotine craving when individuals abstain from smoking (Cook et al., 2004, Leventhal et al., 2009). However, not all smokers report anhedonic symptoms, making it unclear whether sub-clinical reductions in reward function are linked to nicotine craving in the general smoking population. Such an association would suggest that maintenance of smoking in individuals with no overt reward-related pathology may be driven by a mechanism in which subtle reductions in reward sensitivity are linked to increased nicotine craving.
Furthermore, it is unknown if the relationship between craving and reward function is present shortly after smoking. Symptoms of withdrawal and craving emerge after short periods of abstinence, likely contributing to the maintenance of daily smoking behaviors that often involve brief delays between self-administration (Brown et al., 2013, Harrison et al., 2006, Gross et al., 1997). It is unlikely that pharmacological withdrawal alone drives the desire to smoke during this time, as nicotine continues to occupy most of the brain's high affinity β2 nAChRs for up to 5 h following a single smoking episode (Staley et al., 2006). Further, temporal onset of subjective craving is not impacted by acute nicotine administration as compared to placebo (Brown et al., 2013, Gross et al., 1997). Understanding the factors that may relate to nicotine craving within this window, such as blunted reward responsivity, may help elucidate the emergence of craving during brief abstinence.
To clarify the relationship between craving and reward function after a brief period of abstinence, we evaluated nicotine-dependent smokers using a probabilistic reward task (PRT) 4 h after smoking. This task has been used extensively to evaluate individual's ability to modify behavior as a function of monetary (non-drug) reinforcement (AhnAllen et al., 2012, Janes et al., 2015, Pechtel et al., 2013, Pizzagalli et al., 2005, Pizzagalli et al., 2008, Pizzagalli et al., 2009, Santesso et al., 2008) and is sensitive enough to detect not only disruptions in reward processing (Pizzagalli et al., 2005, Pizzagalli et al., 2008), but nicotine-related perturbations in reward sensitivity (Barr et al., 2008, Janes et al., 2015, Pergadia et al., 2014).
In this context, PRT task performance was first compared between briefly abstinent nicotine-dependent smokers and healthy non-smokers to determine whether there were differences in reward responsivity between groups. Next, the relationship between reward responsivity and nicotine craving was evaluated in smokers by correlating PRT task performance with subjective craving as measured by the Questionnaire for Smoking Urges (QSU; Cox et al., 2001), which is a standard assessment of nicotine craving. We hypothesized that smokers with relatively lower non-drug reward responsivity would report more intense nicotine craving, highlighting a link between blunted reward sensitivity and maintenance of nicotine use.
Section snippets
Participants
Fifty-five individuals, 30 nicotine-dependent smokers and 25 non-smokers, completed study procedures at McLean Hospital. All smokers met DSM-IV criteria for current nicotine dependence, which was verified by the Fagerström Test for Nicotine Dependence (FTND; Fagerström, 1978) with an average score of 5.93 (SD = 1.26). All participants were administered the Structured Clinical Interview for DSM Disorders I (SCID-I; First et al., 2002) to identify current and past psychopathology.
Exclusionary
Group differences
Smokers and non-smokers did not differ in age (t(53) = −1.41, p = .17). The groups were significantly different on BDI scores such that the smoking group (M = 3.53, SD = 3.45) scored significantly higher than the non-smoking group (M = 0.50, SD = 1.29; t (52) = −4.44, p = .001). Similarly, the smoking group scored significantly higher on the BDIanhedonia. (M = 0.37, SD = 0.67) compared to the non-smoking group (M = 0.00, SD = 0.00; t (52) = −3.00, p = .001). However, a correlation revealed no significant relationships
Discussion
It is well documented that disrupted reward function and subjective drug craving play a central role in addiction (Blum et al., 2000, Bühler et al., 2010, Garavan et al., 2000, Goldstein et al., 2007, Kalivas and Goldstein, 2005, Koob and Le Moal, 2001, Versace et al., 2012, Volkow et al., 2010). The current findings link these two concepts by showing an association between reduced reward function, as assessed by an objective behavioral measure of reward responsivity, and greater subjective
Role of funding source
This research was supported by National Institute on Drug Abuse grant K01DA029645, by National Institute of Mental Health grants 1R01MH068376 and R01MH101521, and by the Rossano Mind, Brain, and Behavior Pre-Doctoral Fellowship. No funding sources played a role in the study design, collection, analyses and interpretation of the data, in the writing of the report or the decision to submit the paper for publication.
Contributors
Ms. Peechatka and Dr. Janes conceptualized the study. Dr. Pizzagalli provided the signal detection task and critical insight into the analysis and interpretation of results. Ms. Farmer was integral in data collection. Ms. Peechatka, Dr. Janes, and Dr. Whitton analyzed the data. Ms. Peechatka and Dr. Janes drafted the manuscript. Ms. Peechatka consolidated edits from coauthors. All authors approved the final manuscript.
Conflict of interest
Over the past two years, Dr. Pizzagalli has received honoraria/consulting fees from Otsuka America Pharmaceutical, Pfizer, and Servier for activities unrelated to this project. All other authors declare no conflicts of interest.
References (57)
- et al.
Nicotine dependence and smoking topography among black and white women
Res. Nurs. Health
(1997) - et al.
The relationship between reward-based learning and nicotine dependence in smokers with schizophrenia
Psychiatry Res.
(2012) - et al.
The influence of smoking on reward responsiveness and cognitive functions: a natural experiment
Addiction
(1997) - et al.
Where is the pleasure in that? Low hedonic capacity predicts smoking onset and escalation
Nicotine Tob. Res.
(2012) - et al.
A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence
Biol. Psychiatry
(2008) - et al.
Comparison of beck depression inventories – IA and – II in psychiatric outpatients
J. Pers. Assess.
(1996) - et al.
The reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors
J. Psychoact. Drugs
(2000) - et al.
Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum
Psychopharmacology
(2013) - et al.
Nicotine dependence is characterized by disordered reward processing in a network driving motivation
Biol. Psychiatry
(2010) - et al.
Brain reward system activity in major depression and comorbid nicotine dependence
J. Pharmacol. Exp. Ther.
(2002)
Hedonic capacity, cigarette craving, and diminished positive mood
Nicotine Tob. Res.
Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings
Nicotine Tob. Res.
Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat
Psychopharmacology
A double-blind placebo controlled experimental study of nicotine: I – Effects on incentive motivation
Psychopharmacology
A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors
Schizophr. Res.
Schizophrenia and smoking: an epidemiological survey in a state hospital
Am. J. Psychiatry
Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging
Am. J. Psychiatry
The effect of bupropion sustained-release on cigarette craving after smoking cessation
Clin. Ther.
Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment
Addict. Behav.
Carbon monoxide and smoking behavior
Addict. Behav.
Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-Patient Edition. Biometrics Research
Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli
Am. J. Psychiatry
Smoking, smoking cessation, and major depression
JAMA
Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction?
Am. J. Psychiatry
Nicotine-containing versus de-nicotinized cigarettes: effects on craving and withdrawal
Pharmacol. Biochem. Behav.
The early time course of smoking withdrawal effects
Psychopharmacology
Expired air carbon monoxide accumulation and elimination as a function of number of cigarettes smoked
Addict. Behav.
Reward responsiveness varies by smoking status in women with a history of major depressive disorder
Neuropsychopharmacology
Cited by (20)
Momentary gustative-olfactory sensitivity and tonic heart rate variability are independently associated with motivational behavior
2023, International Journal of PsychophysiologyComparing the reward value of cigarettes and food during tobacco abstinence and nonabstinence
2019, Drug and Alcohol DependenceCitation Excerpt :Examinations of the relationship between craving and reward value of cigarettes may help clarify the motivation for drug and non-drug rewards. Some studies have found that, during abstinence, there is a negative correlation between drug craving and non-drug reward variables (e.g., non-drug reward responsiveness and anticipation; Peechatka et al., 2015; Sweitzer et al., 2014; Wrase et al., 2007). This supports the argument that withdrawal is associated with increased craving and motivation for drugs and decreased value of non-drug rewards.
Inhibitory Plasticity of Mesocorticolimbic Circuits in Addiction and Mental Illness
2018, Trends in NeurosciencesCitation Excerpt :Multiple stimuli (including stress, pain, and withdrawal from nicotine or morphine) trigger KCC2-mediated plasticity that leads to blunted behavioral and neural reward sensitivity, but that blunted reward sensitivity also commonly promotes drug self-administration [31,62,63,65]. In humans, attenuated behavioral and neuronal responses to rewards predict the onset, escalation, and relapse in drug abuse, implying that drug taking may partially alleviate disrupted reward function caused by stress, chronic pain, drug withdrawal, or depressive disorders [67–73]. We hypothesize that KCC2-mediated synaptic plasticity in VTA GABA neurons represents one mechanistic pathway linking attenuated reward sensitivity to increased motivation for drug intake.
Current major depression is associated with greater sensitivity to the motivational effect of both negative mood induction and abstinence on tobacco-seeking behavior
2017, Drug and Alcohol DependenceCitation Excerpt :The second explanation is that depressed smokers are more sensitive to a wide range of correlated adverse triggers for smoking. In fact, a wide range of adverse states (in addition to negative affect and abstinence) have been shown to augment tobacco motivation including stress/anxiety (Owens et al., 2014), rumination (Dvorak et al., 2011), anger/hostility (Quinn et al., 2014; Zuo et al., 2016), cognitive dysfunction (Hall et al., 2015), fatigue/sleepiness (Hamidovic and de Wit, 2009) and reward hyposensitivity (Peechatka et al., 2015). Although it remains to be tested whether depressed smokers are more sensitive to all of these adverse triggers, our finding that they are more sensitive to both mood induction and abstinence suggests this may be the case.
Paradise Lost: A New Paradigm for Explaining the Interaction Between Neural and Psychological Changes in Nicotine Addiction Patients
2017, Addictive Substances and Neurological Disease: Alcohol, Tobacco, Caffeine, and Drugs of Abuse in Everyday Lifestyles