Inhibitory control dysfunction in nicotine dependence and the influence of short-term abstinence
Introduction
Current models of substance dependence suggest that deficits in executive control are critical to ongoing drug use (Jentsch and Taylor, 1999). In particular, inhibitory control (IC), which is the ability to inhibit a pre-potent response, may be especially involved in maintaining drug dependence (Goldstein and Volkow, 2002, Lubman et al., 2004). IC impairment is prevalent within varying forms of drug-dependence, including alcohol, methamphetamine and cocaine dependence (Fillmore and Rush, 2002, Li et al., 2009, Lubman et al., 2004, Monterosso et al., 2005). The reliability of IC dysfunction in individuals dependent on substances with widely differing neurochemical profiles suggests IC dysfunction is a common feature of addiction and would therefore feature similarly in nicotine dependence.
Research examining IC performance in nicotine dependence has to date yielded a varied set of findings. Nicotine dependent individuals demonstrate impaired performance on measures of impulsivity, such as delay discounting tasks, in which smaller immediate monetary rewards are favoured over larger but delayed rewards (Bickel et al., 1999, Mitchell, 1999, Reynolds et al., 2004); and risky financial decision making, in which potentially higher pay-offs are chosen while accepting the increased risk of losing everything (Lejuez et al., 2003). For example, Yakir et al. (2007) reported a selective deficit in impulsivity within both current and past smokers when compared to controls. However, studies measuring IC over a pre-potent motor response using the Go/No-go and stop signal tasks (Dinn et al., 2004, Spinella, 2002, Yakir et al., 2007) have not reliably demonstrated IC impairment in comparison to control populations. For example, Spinella (2002) found that IC performance on a Go/No-go task was negatively correlated with smoking behaviour, where levels of IC deficit were proportional to smoking severity. In contrast, Dinn et al. (2004) also administered the Go/No-go task and found no difference in performance between smokers and non-smokers.
The mixed findings of past research may be due to factors that independently affect IC function. Demographic variables that influence IC, such as age (Kramer et al., 1994) have not always been controlled. For example, Spinella's (2002) sample varied in cigarette use (levels not reported in the paper) and age (range = 19–70 years, mean = 31.1 SD = 16.7), with the latter variable not used as a covariate in the correlation between nicotine use and IC performance. Similarly, because most of these studies have recruited college or community samples, they have not always screened for IC confounds such as history of traumatic brain injury (Dimoska-Di Marco et al., 2011) or other types of drug abuse (Fillmore and Rush, 2002, Li et al., 2009, Monterosso et al., 2005).
IC performance also appears sensitive to variation in the duration of nicotine abstinence prior to cognitive testing. In other dependent populations, administration of a drug of dependence (e.g., cocaine or heroin) reduces levels of IC deficit otherwise present in dependent individuals, with short-term abstinence inducing the opposite effect (Goldstein and Volkow, 2011). In parallel to these findings, acute nicotine administration reverses otherwise prevalent IC deficits in ADHD (Potter and Newhouse, 2004) and abstinence from cigarettes in an otherwise healthy population has been associated with decreased IC performance (Harrison et al., 2009). As such, satiated smokers may have acutely elevated IC performance that masks underlying IC deficits (Dawkins et al., 2007). However the influence of nicotine abstinence on the presence/absence of IC deficits in past studies remains unclear, as few have approached abstinence as an independent factor interacting with IC ability.
Given the small number of studies and mixed findings, the aim of the present study was to examine IC function in nicotine dependence whilst controlling for demographic and drug use confounds. To examine the influence of nicotine abstinence on IC dysfunction we also conducted a within-subject comparison between nicotine satiation and short-term, 10-h abstinence.
Study 1 compared a group of dependent smokers to a control group of non-smokers on IC performance using a stop signal task (Logan et al., 1997). To limit acute effects of nicotine, dependent smokers completed the SST following 3-h of nicotine abstinence. It was hypothesised that after controlling for variables that had confounded previous studies (demographics, other drug use, brain injury), nicotine dependence would be associated with poorer IC in comparison to controls, indicated by higher stop signal reaction time (SSRT). Study 2 examined the influence of nicotine abstinence on IC performance by comparing dependent nicotine smokers’ SSRT after a 10-h period of abstinence to performance at nicotine satiation. It was hypothesised that in dependent smokers inhibitory performance would be significantly poorer following prolonged nicotine abstinence than at satiation.
Section snippets
Study 1
Participants: 37 dependent cigarette smokers (11 females; mean age 23.70; SD = 4.32) and 36 non-smokers (13 females; mean age 23.14; SD = 4.85) were recruited for the study. Inclusion in the smokers group required smoking 15 or more cigarettes a day for a minimum of two years. Non-smoking participants had each consumed less than 10 cigarettes in their lifetime. Exclusion criteria for both groups included a history of neurological or psychiatric disorders, current use of psychotropic medication or
Discussion
Study 1 compared inhibitory control performance of nicotine dependent and matched non-dependent controls using a stop signal task (SST), with the nicotine dependent group abstaining from nicotine for 3-h prior to testing. Contrary to our hypothesis, IC performance did not significantly differ between the groups. Using the same SST task, Study 2 compared IC performance in nicotine dependent individuals following a period of 10-h abstinence with nicotine satiation. Consistent with our hypothesis,
Role of funding source
The project was supported by the Australian National Health and Medical Research Council grant to R.H. (ID: 1050766). The NHMRC did not contribute in any way to study design; data collection, analysis or interpretation; the writing of the report; or submitting the manuscript for publication.
Contributors
R.H., L.H., and D.G.M designed the study and developed the protocol, K.C-W. and R.H. undertook data analysis and wrote the paper, L.H. and D. G. M. recruited participants, administered cognitive tests and assisted in literature revision. All authors contributed to drafts of the manuscript.
Conflict of interest statement
No conflict declared.
Acknowledgements
The authors would like to thank Drs Daniel Upton and Stefan Bode for helpful comments on the manuscript and to all the participants who graciously contributed to the research.
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