Attenuated adrenocortical and blood pressure responses to psychological stress in ad libitum and abstinent smokers
Introduction
Acute stress activates adrenocortical and sympathetic systems McEwen and Stellar, 1993, Chrousos and Gold, 1992, Mills and Dimsdale, 1992. Under stress, the hypothalamic–pituitary–adrenocortical (HPA) system produces corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus, which in turn stimulates the release of the adrenocorticotropic hormone (ACTH) from the anterior pituitary Owens and Nemeroff, 1991, Dallman, 1993, al'Absi and Arnett, 2000, Koob et al., 1993. ACTH travels through the circulatory system to the adrenal cortex, stimulating the release of cortisol (Petrudz and Merchenthaler, 1992). Cortisol plays a significant role as a modulator of the central nervous system during stress McEwen and Sapolsky, 1995, Kreek and Koob, 1998, al'Absi et al., 2002b. It interacts with several neurotransmitters that are modulated by nicotine or mediate nicotine's effects, including acetylcholine, norepinephrine, dopamine, vasopressin, and beta-endorphin (Koob and Le Moal, 1997). Stress also produces various sympathetic changes, including increased blood pressure (BP), heart rate (HR), and catecholamine production Mills and Dimsdale, 1992, Lovallo et al., 1990, Cacioppo, 1994, Christensen, 1994, which possibly mediate effects of stress on smoking and relapse Epping-Jordan et al., 1998, Kreek and Koob, 1998, Pomerleau and Pomerleau, 1991, Roth et al., 1988.
The acute effects of nicotine on adrenocortical and cardiovascular functions have been investigated in several laboratory studies Fuxe et al., 1989, Davis, 1999, Davis and Matthews, 1990, Pomerleau and Pomerleau, 1991, Pomerleau et al., 1983, Seyler et al., 1984, Dembroski et al., 1985, MacDougall et al., 1986, Wilkins et al., 1982, Houlihan et al., 1999. An additive effect of nicotine and acute stress has been documented on cortisol production (Pomerleau and Pomerleau, 1991) and BP Dembroski et al., 1985, MacDougall et al., 1986. Effects of nicotine on the HPA axis are mediated by nicotine's effects on multiple central nervous system pathways, although specific mechanisms have not been elucidated. Nicotine stimulates vasopressin secretion, which, in combination with CRH, leads to ACTH release. It also stimulates cholinergic receptors in the hypothalamus, particularly the PVN, causing the release of CRH, which starts the HPA cascade, leading to the production of cortisol from the adrenal cortex Fuxe et al., 1989, Pomerleau and Pomerleau, 1991, Seyler et al., 1984. Chronic administration may lead to prolonged HPA activation, although the degree to which tolerance develops to the HPA effects of nicotine is not clear.
Little is known about cortisol responses to stress after extended periods of smoking or how these responses may be modified by short-term abstinence. It is possible that adrenocortical responses to stress in smokers are altered after abstinence, and that these abstinence-related changes enhance the intensity of withdrawal symptoms under acute stressful events, contributing to relapse Kreek and Koob, 1998, Piazza and Le Moal, 1998. Determining the stress response profile in abstinent smokers should help elucidate the role of stress-related physiological changes in withdrawal symptoms. This should also provide information related to the extent to which acute stress may contribute to alteration in the rewarding properties of nicotine (Piazza and Le Moal, 1998).
While some studies have reported that smokers show smaller salivary cortisol responses to laboratory stressors when compared to nonsmokers Kirschbaum et al., 1993b, Roy et al., 1994, others report no differences Baron et al., 1995, Tersman et al., 1991. These discrepancies may stem from differences in experimental design. For example, smokers may vary in terms of the level of nicotine dependence and comorbid psychopathology. It is also possible that the inconsistent cortisol findings reflect variability in the length of abstinence and, therefore, the severity of withdrawal symptoms. Focusing on BP responses, one study (Tsuda et al., 1996) attempted to address this issue and found that smokers who were abstinent from tobacco overnight had a lower diastolic BP baseline, but greater responses to behavioral stressors than ad libitum smokers and nonsmokers. We recently reported that smokers had greater systolic BP responses to cognitive challenges after overnight abstinence than after the ad libitum condition in a within-subject, abstinent-smoking, counterbalanced design (al'Absi et al., 2002a). There was no difference in cortisol concentrations between the abstinence and ad libitum smoking conditions (al'Absi et al., 2002a).
Studies that have addressed these questions so far have suffered from several limitations, including small sample size, exclusion of women, and minimal or no control of effects of time of day on the dependent measures, especially cortisol. Effects of acute stress and smoking abstinence have also not been directly compared with those of nonsmokers, and no systematic work has focused on separating the pharmacological effects of smoking from effects of abstinence. Furthermore, only brief cognitive challenges were used in the earlier studies. A better assessment of the effects of acute stress requires the use of stressors that are socially relevant with significant effects on the HPA axis (al'Absi et al., 1997). Socially relevant stressors are more ecologically valid challenges compared with structured and brief psychomotor or mental challenges. Socially salient stressors may better simulate situations where smokers may encounter interpersonal conflicts or challenges that might increase their risk of smoking or relapse. Assessment of effects of stress on cortisol production also requires the use of rest day control design to provide appropriate within-subject control that accounts for effects of time of the day on HPA activity. This is an important element of control in light of the clear diurnal variation of cortisol productions (Weitzman et al., 1971).
The purpose of this study was to determine alterations in psychophysiological and adrenocortical responses to behavioral stress in dependent smokers compared to nonsmokers, and to assess effects of short-term abstinence on responses to acute stress. We predicted that, compared to ad libitum smokers and nonsmokers, abstinent smokers would exhibit enhanced responses to stress. Smokers and nonsmokers participated in two counterbalanced sessions (rest and stress) separated by a minimum of 2 days. Smokers were assigned to one of two conditions: abstinence from smoking and all nicotine-containing products the night before and the day of each laboratory session, or smoking ad libitum.
Section snippets
Participants
Thirty-eight smokers (17 men and 21 women) and 32 nonsmokers (14 men and 18 women) were recruited by newspaper advertisements and posters placed around the university community. Subjects underwent a screening session, which included a brief medical history, assessment of behavioral habits (including history of smoking, alcohol, and drug use), and measurement of height and weight. Participants had to meet the following criteria: (1) no regular use of prescribed or over-the-counter medications;
Participant characteristics
Table 1 shows participants' characteristics. All three groups did not differ in age, height, weight, or education (Fs<1). The two smoking groups reported drinking more coffee than nonsmokers [Fs(2,60)>10.30, Ps<.001]. There was also a trend toward greater physical activity in nonsmokers [F(2,60)=3.00, P=.06]. Groups did not differ in reported depression, anxiety, or perceived stress (Fs<1), as shown in Table 1.
The two smoking groups did not differ in level of nicotine dependence as assessed by
Discussion
This study compared adrenocortical and cardiovascular responses to stress among smokers who continued to smoke ad libitum, abstinent smokers, and nonsmokers, and included a rest day control session to account for diurnal changes in salivary cortisol. While both groups of smokers showed higher prevailing cortisol levels than nonsmokers, neither showed an appreciable cortisol response to stress. Smokers also showed attenuated systolic BP responses to the public-speaking stressor. Although
Acknowledgements
We thank Todd Amunrud, Katie Bellmont, Kevin Sullivan, and Andrew Cumings for assistance with data collection and management. We thank Clemens Kirschbaum of the Institute of Physiological Psychology, University of Düsseldorf, Düsseldorf, Germany. We thank Paul Pentel of the University of Minnesota and the Hennepin County Medical Center for his assistance in assaying salivary cotinine samples. This research was supported, in part, by grants to the first author from the National Institute on Drug
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