Sensitivity to monetary reward is most severely compromised in recently abstaining cocaine addicted individuals: A cross-sectional ERP study

Abstract

Recent studies suggest that drug-addicted individuals have a dampened cortical response to non-drug rewards. However, it remains unclear whether recency of drug use impacts this impairment. Therefore, in this event-related potential study, recency of cocaine use was objectively determined by measuring cocaine in urine on study day. Thirty-five individuals with current cocaine use disorder [CUD: 21 testing positive (CUD+) and 14 testing negative (CUD−) for cocaine in urine] and 23 healthy controls completed a sustained attention task with graded monetary incentives (0¢, 1¢ and 45¢). Unlike in controls, in both CUD subgroups P300 amplitude was not modulated by the varying amounts of money and the CUD− showed the most severe impairment as documented by the lowest P300 amplitudes and task accuracy. Moreover, while recency of drug use was associated with better accuracy and higher P300 amplitudes, chronic drug use was associated with lower sensitivity to money. These results extend our previous findings of decreased sustained sensitivity to monetary reward in CUD+ to recently abstaining individuals, where level of impairment was most severe. Taken together, these results support the self-medication hypothesis, where CUD may be self-administering cocaine to avoid or compensate for underlying cognitive and emotional difficulties albeit with a long-term detrimental effect on sensitivity to non-drug reward.

Introduction

A typical pattern of drug addiction in humans is characterized by intermittent periods of abstinence from drug-taking followed by increased craving and relapse (Gawin, 1991, O'Brien, 1997). These stages in drug addiction are thought to result from enduring drug-induced neuroadaptations within the mesocorticolimbic dopaminergic reward circuitry, although such neural compromises may also precede, and predispose to, the development of drug addiction (Goldstein and Volkow, 2002, Shalev et al., 2002, Kalivas and McFarland, 2003, Volkow et al., 2004). Irrespective of the direction of causality, dysregulated sensitivity to reward has been shown in drug-addicted individuals. For example, using functional magnetic resonance imaging (fMRI), we reported a compromised cortical sensitivity to monetary reward on a sustained attention task in individuals with cocaine use disorders (CUD) (Goldstein et al., 2007a); similar results have since been reported in alcoholics (Chen et al., 2007) and pathological gamblers (de Ruiter et al., 2009).

In a validation study (Goldstein et al., 2008), we investigated the P300 event-related potential (ERP), shown to have a core role in processing the incentive value of reinforcers on select tasks in healthy individuals (Hajcak et al., 2005, Sato et al., 2005, Wu and Zhou, 2009), and reported that CUD failed to show the expected graded P300 response to different levels of monetary reward (i.e., 45¢ > 0¢) (Goldstein et al., 2008). In contrast to other ERP studies in CUD (Biggins et al., 1997, Bauer, 2001, Gooding et al., 2008), and in opioid (Papageorgiou et al., 2004), alcohol (Fein and Chang, 2006) and nicotine (Anokhin et al., 2000) dependent individuals, however, we did not observe overall reduced P300 amplitudes in our sample.

Variability in recency of drug use may have contributed to this inconsistency in the P300 results. While most other studies recruited abstaining subjects from treatment facilities (Biggins et al., 1997, Bauer, 2001, Gooding et al., 2008), we recruited subjects abstaining for less than 4 days prior to study day (Goldstein et al., 2008). Indeed, abstinence has been shown to impact several cognitive [learning, memory and executive functions (Woicik et al., 2009)] and emotional [sustained emotional reactivity to drug cues (Dunning et al., 2011)] functions that are essential for processing the incentive value of reinforcers.

Therefore, the goal of the current study was to investigate contribution of abstinence length in current cocaine users to the monetary reward-elicited P300 amplitudes. For this purpose, in addition to the 36 subjects [18 CUD; all positive for cocaine in urine (CUD+) and 18 controls] that were included in our previous report (Goldstein et al., 2008), CUD who were negative for cocaine in urine (CUD−) were also included. Note that all CUD used crack/cocaine in the past 30 days, and that inclusion of the CUD− subgroup is entirely new to this study.

Given results by others (Biggins et al., 1997, Bauer, 2001, Papageorgiou et al., 2004, Fein and Chang, 2006, Gooding et al., 2008) and our prior neuropsychological results where we reported that cognitive impairment was most severe in CUD− as compared to CUD+ (Woicik et al., 2009), we a priori hypothesized that the recently abstinent group (with less recent cocaine use) will manifest the most severe reward-related P300 impairments. In addition to the P300, we explored earlier ERP components relevant to our task: the fronto-central P200, that has recently been described in the context of task relevance, attention and motivational spillover (Carretie et al., 2001a, Holroyd and Coles, 2002, Potts, 2004, Potts et al., 2006, Holroyd et al., 2008, Franken et al., 2010), and the fronto-central N200 that has been associated with biologically significant events (Campanella et al., 2002), stimulus novelty (Daffner et al., 2000) and top–down cortical inhibition (Folstein and Van Petten, 2008). Analyses pertaining to these earlier components were exploratory.