Negative affective states and cognitive impairments in nicotine dependence

Abstract

Smokers have substantial individual differences in quit success in response to current treatments for nicotine dependence. This observation may suggest that different underlying motivations for continued tobacco use across individuals and nicotine cessation may require different treatments in different individuals. Although most animal models of nicotine dependence emphasize the positive reinforcing effects of nicotine as the major motivational force behind nicotine use, smokers generally report that other consequences of nicotine use, including the ability of nicotine to alleviate negative affective states or cognitive impairments, as reasons for continued smoking. These states could result from nicotine withdrawal, but also may be associated with premorbid differences in affective and/or cognitive function. Effects of nicotine on cognition and affect may alleviate these impairments regardless of their premorbid or postmorbid origin (e.g., before or after the development of nicotine dependence). The ability of nicotine to alleviate these symptoms would thus negatively reinforce behavior, and thus maintain subsequent nicotine use, contributing to the initiation of smoking, the progression to dependence and relapse during quit attempts. The human and animal studies reviewed here support the idea that self-medication for pre-morbid and withdrawal-induced impairments may be more important factors in nicotine addiction and relapse than has been previously appreciated in preclinical research into nicotine dependence. Given the diverse beneficial effects of nicotine under these conditions, individuals might smoke for quite different reasons. This review suggests that inter-individual differences in the diverse effects of nicotine associated with self-medication and negative reinforcement are an important consideration in studies attempting to understand the causes of nicotine addiction, as well as in the development of effective, individualized nicotine cessation treatments.

Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

“…Nicotine was infused through subcutaneous osmotic minipumps at concentrations of 14 and 40 mg/kg/day (Model 2004, ALZET, Palo Alto, CA). Doses were chosen based on previous reports of effects in mice (Stoker et al 2008; Portugal and Gould 2009; Hall et al 2015). …”

“…It is now commonly accepted that the difficulty of smoking cessation is, in part, due to the cognitive deficits associated with nicotine withdrawal (Hall et al 2015). Patients report difficulty concentrating and confusion with quantified nicotine withdrawal-induced impairments to working memory, attention, response inhibition, reward processing, and reaction time (Hughes 2007; McClernon et al 2015; van Enkhuizen and Young 2016).…”

“…In fact, some of these cognitive impairments, including attention deficits and impulse control, before and during withdrawal can predict relapse (Pomerleau et al 2003; Dolan et al 2004; Rukstalis et al 2005; Krishnan-Sarin and Reynolds 2007; Culhane et al 2008; Powell et al 2010). Understanding the mechanism(s) underlying withdrawal-induced cognitive deficits may be key toward developing targeted treatments that will remediate these deficits and aid quit attempts (Hall et al 2015). …”

Insight into the Potential Factors That Promote Tobacco Use in Vulnerable Populations

“…Following chronic tobacco use, withdrawal from nicotine produces a milieu of withdrawal symptoms including physical signs, negative affective states and cognitive deficits (see Table 1; [4]). Growing evidence suggests that the physical signs of withdrawal are mechanistically distinct from negative affective states.…”

“…Studies using IV and oral SA procedures have also shown that nicotine intake is higher in adolescent versus adult rats [23][24][25][26][27][28] and mice [29]. High doses of For a recent and comprehensive review of the physical and affective states produced by withdrawal in rodents and humans, the reader is referred to Hall et al [4] nicotine also produce aversive effects that are lower in adolescent versus adult rats [18,30]. With regard to withdrawal, clinical studies have revealed that young smokers exhibit milder symptoms of withdrawal during abstinence from smoking [31], and they are less responsive to cessation approaches that alleviate withdrawal [32][33][34].…”