Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers

Highlights

• Craving and reward responsivity were examined in smokers 4 h after smoking.

• Reward responsivity did not differ between briefly abstinent smokers and non-smokers.

• In smokers, greater cigarette craving was associated with blunted reward responsivity.

Abstract

Background

Dysfunctional reward processing leading to the undervaluation of non-drug rewards is hypothesized to play a crucial role in nicotine dependence. However, it is unclear if blunted reward responsivity and the desire to use nicotine are directly linked after a brief period of abstinence. Such an association would suggest that individuals with reduced reward responsivity may be at increased risk to experience nicotine craving.

Methods

Reward function was evaluated with a probabilistic reward task (PRT), which measures reward responsivity to monetary incentives. To identify whether smoking status influenced reward function, PRT performance was compared between non-depressed, nicotine-dependent smokers and non-smokers. Within smokers, correlations were conducted to determine if blunted reward responsivity on the PRT was associated with increased nicotine craving. Time since last nicotine exposure was standardized to 4 h for all smokers.

Results

Smokers and non-smokers did not differ in reward responsivity on the PRT. However, within smokers, a significant negative correlation was found between reward responsivity and intensity of nicotine craving.

Conclusions

The current findings show that, among smokers, the intensity of nicotine craving is linked to lower sensitivity to non-drug rewards. This finding is in line with prior theories that suggest reward dysfunction in some clinical populations (e.g., depressive disorders, schizophrenia) may facilitate nicotine use. The current study expands on such theories by indicating that sub-clinical variations in reward function are related to motivation for nicotine use. Identifying smokers who show blunted sensitivity to non-drug rewards may help guide treatments aimed at mitigating the motivation to smoke.

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.