Prior research indicates that alcohol-dependent individuals demonstrate a blunted stress system response following an acute psychosocial stressor (Adinoff et al., 2005a
; Lovallo et al., 2000
). However, variability in stress reactivity in this population and individual factors, such as nicotine use, that may contribute to this variability have not been systematically examined. The current study was designed to assess the role of nicotine on subjective, cardiovascular and salivary cortisol response to a psychosocial stressor. To that end, subjects received either a placebo, low dose (7 mg) or high dose (14 mg for women, 21 mg for men) and performed a psychosocial stress protocol consisting of two 4-minute speeches (al'Absi et al., 1997
). Self-reported measures of nicotine dependence and withdrawal were also completed concurrently with the stressor.
Consistent with previous work (Bernardy et al., 1996
; Junghanns et al., 2003
; Lovallo et al., 2000
), substance-dependent individuals failed to demonstrate an increase in salivary cortisol to the psychosocial stressor although they reported elevated cardiovascular measures and self-reported distress. This disconnection between ‘blunted’ cortisol levels and ‘elevated’ self-reported distress and cardiovascular measures following a psychosocial stressor are similar to those of Errico et al. (1993)
. The study of Errico et al. (1993)
showed that while alcoholics displayed blunted cortisol levels following a psychosocial stressor, their self-reported distress and cardiovascular measures were equivalent to those of community controls.
Comparisons in the current study also extended these findings of Errico et al. (1993)
. Specifically, substance-dependent individuals who received nicotine reported less positive affect (high dose) and more negative affect (high and low doses) following the psychosocial stressor when compared with those who received placebo. While an explanation for these findings is not immediately apparent, it could be suggested that higher level brain areas involved in appraisal and emotional response to the stressor may be activated by acute nicotine administration (Panknin et al., 2002
). Thus, greater negative affect following the psychosocial stressor may reflect a normalization of the poststress emotional response as negative emotional responses are blunted in alcohol-dependent individuals (Salloum et al., 2007
). Why nicotine had similar normalization in salivary cortisol levels for only a minority of substance-dependent individuals, as discussed below, remains an empirical question.
Also intriguing is the finding that substance-dependent individuals who received placebo demonstrated few signs of acute nicotine withdrawal. For instance, self-reported withdrawal symptoms scores ranged from 3 to 5 (out of a possible score of 33) in those who received placebo and did not differ from those who received the active dose either at baseline, or following the psychosocial stressor. Similarly, baseline physiological measures taken just prior to the stressor did not differ between groups. Self-reported anxiety symptoms were also below the range of clinical significance, although slight group differences did exist.
Several explanations exist for the absence of nicotine withdrawal symptomatology in these nicotine-dependent subjects. First, the time course may not have been sufficient to allow for the development of a nicotine withdrawal syndrome (Hughes, 2007
; Shiffman et al., 2006
). Subjects in the current study abstained from nicotine for less than 24 h, which may be too limited a time period for subjects to experience nicotine withdrawal symptoms, which peak in 2–5 days following cessation (Hughes, 2007
; Shiffman et al., 2006
). Second, the laboratory setting may be devoid of environmental contexts that prompt cigarette craving (Conklin, 2006
; Van Gucht et al., 2010
). Although the association between environmental contexts, cigarette craving and onset of nicotine withdrawal symptoms is unclear, the literature supports that these constructs may be related (Conklin, 2006
; Shiffman and Paty, 2006
; Van Gucht et al., 2010
). Third, the task demands may have cognitively distracted subjects from physiological withdrawal symptoms. Although untested, this phenomenon has much anecdotal support. Arguably distinct, physical exercise also promotes reduced withdrawal symptoms, suggesting that withdrawal symptoms are not ubiquitous following smoking cessation (Taylor et al., 2007
). It is possible that cognitive distraction produces a similar outcome, as may be the case in the current study. Regardless of the underlying mechanism, the similarity of nicotine withdrawal symptomatology in active and placebo groups suggests that the nicotine results discussed are not dependent upon this factor.
Using standard statistical techniques, it appears that nicotine had no effect on cortisol activation following a psychosocial stressor. However, distribution data suggested the need for focused analyses. First, the individuals who received a high dose of nicotine were compared with those who received placebo following the psychosocial stressor (+20 min). Differences between these two doses produced a statistical trend at P
= 0.08, where salivary cortisol levels were higher in those who received nicotine compared with placebo. Second, a profile analysis was used to characterize distribution data (Tabachnick and Fidell, 1989
, p.453). Through this technique, four groups of salivary cortisol responses were identified. In contrast to the overall findings based on mean comparisons, profile analyses showed that 33% of the substance-dependent individuals responded to the stressor, having significantly higher cortisol levels than at baseline. This group of responders displayed similar salivary cortisol level responses as nicotine-dependent community controls, were more likely to be alcohol dependent and had received the high dose of nicotine in the current study. Thus, in spite of the many drug, subgroup similarities in baseline and stress responsivity measures, it is notable that the alcohol-dependent subjects are most sensitive to nicotine effects in the current study, albeit in the substantial minority of subjects who responded to the psychosocial stressor. Alcohol-dependent individuals have also been shown to be differentially sensitive to the neurocognitive enhancing properties of transdermal nicotine administration (see Ceballos et al., 2005
and Nixon et al., 2007
for further discussion).
The mechanism of action of nicotine's effects on salivary cortisol levels in alcohol-dependent individuals could be attributed to either peripheral or centralized factors. While nicotinic receptors are abundant in the adrenal gland suggesting a peripheral mechanism (Bornstein and Chrousos, 1999
; Tsigos and Chrousos, 2002
), the cognitive appraisal of the psychological threat during the psychosocial stress protocol also suggests centralized mechanisms. The concept of allostasis, or ‘maintenance of stability outside the normal homeostatic range’ (Koob and Le Moal, 2001
), may describe the stress system dysregulation demonstrated by blunted salivary cortisol levels and subsequent possible amelioration by nicotine. These findings strengthen the conclusion regarding individual variability in the integrity of the stress system and its potential susceptibility to adaptive deficits in homeostatic load accommodation (allostatis).
The limitations of the current study leave several issues to be addressed in future research. First, logistical considerations limited the study design to a between-subjects investigation; that is, subjects who received placebo patches were compared with a second group who received nicotine. Results of the current study would be strengthened if they were replicated by future studies including a within-subjects design. Additionally, although saliva collection is a widely accepted methodology for measurement of cortisol levels, future studies addressing the heterogeneity of cortisol levels in substance-dependent individuals should include measures of both plasma and salivary cortisol. Lastly, while the community controls provided an important comparison group in the current study, future studies would be strengthened by inclusion of a greater number of subjects in this group.