Nicotine and the central nervous system: Biobehavioral effects of cigarette smoking

The effects of nicotine, like those of other drugs with potential for abuse and dependence, are centrally mediated. The impact of nicotine on the central nervous system is neuroregulatory in nature, affecting biochemical and physiological functions in a manner that reinforces drug-taking behavior. Dose-dependent neurotransmitter and neuroendocrine effects occur as plasma nicotine levels rise when a cigarette is smoked. Circulating levels of norepinephrine and epinephrine increase, and the bioavailability of dopamine is altered as well. Among the neuroendocrine effects are release of arginine vasopressin, [beta]-endorphin, adrenocorticotropic hormone, and cortisol. Notably, several of these neurochemicals are psychoactive and/or known to modulate behavior. Thus, affective states or cognitive demands may be favorably modified (at least temporarily) by nicotine intake. When nicotine is inhaled, the neuroregulatory effects just described are immediately available and the reinforcing effects of the drug are maximized. On the other hand, nicotine gum and most other nicotine replacement vehicles in current use have a slower onset of action, resulting in less reinforcement value. Recent data suggest that smoking cessation rates may be optimized by tailoring the dose of nicotine replacement (for example, 2 or 4 mg of nicotine gum) to the individual degree of nicotine dependence. In view of the dynamic interactions between the neuroregulatory effects of nicotine and a host of environmental conditions, nicotine replacement therapy is best carried out in combination with behavior modification techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29947/1/0000305.pd

Individual differences in sensitivity to nicotine: Implications for genetic research on nicotine dependence

Recent evidence suggests that cigarette smoking has a heritability index around 53%. While related research on underlying mechanisms also supports the idea that genetic factors contribute to nicotine dependence—as well as to cofactors such as substance use and mood disorders—the nature of the behavioral traits and biological capacity for reinforcement that constitutes vulnerability to nicotine dependence is not well understood. The present review explores the problem of why some people become highly nicotine dependent, others develop a pattern of occasional use, and still others avoid the drug entirely despite extensive exposure and widespread experimentation with tobacco in the population. Recent research—both infrahuman and human—suggests that vulnerability to nicotine dependence is related to high initial sensitivity to nicotine and that the development of tolerance is more rapid and self-administration more extensive in such individuals. Relevant findings from neuroscience and biobehavioral research are reviewed in order to identify variables and methodologies that might improve the reliability and validity of behavioral and molecular genetic studies on cigarette smoking. The integration of research in these areas may lead to new insights in the understanding of nicotine dependence as well as to improved techniques for prevention and treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44111/1/10519_2005_Article_BF02196925.pd

Cortisol response to a psychological stressor and/or nicotine

The effects of a psychological stressor and nicotine upon corticosteroid release were investigated using a full factorial, repeated-measures design in eight moderate smokers. Sessions involved the presentation of either competitive mental arithmetic or reading aloud and either smoking a usual cigarette or sham smoking. Self-reported anxiety increased after exposure to competitive mental arithmetic, confirming the stressfulness of the procedure. Cortisol levels increased significantly in response to psychological stress and showed a trend towards a significant elevation over time in response to nicotine self-administration. The two manipulations in combination produced additive effects upon plasma cortisol. These findings underscore the usefulness of the corticosteroid response as a marker of the impact of different procedures and suggest that it may provide an indicator for exploring the mechanisms by which nicotine-stress interactions are mediated. Systematic research that varies temporal and other parameters involving nicotine and various stressors will be needed to resolve inconsistencies in the literature on smoking and anxiety in the context of stress.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28597/1/0000405.pd

Euphoriant effects of nicotine in smokers

Two studies were conducted to replicate and extend previous demonstrations of smoking-induced, dose-related reports of euphoria, and to confirm this relationship using measures of plasma nicotine. In experiment 1, overnight-deprived subjects, in three different sessions, smoked ultralow-, high-nicotine, and usualbrand cigarettes. In experiment 2, ultralow-, medium-, and high-nicotine cigarettes were used, and plasma nicotine was measured. In both studies, subjects were asked to depress a button during euphoric sensations. Number of sensations for the ultralow-nicotine cigarette was significantly lower than for the high-nicotine cigarette in the first study, and than for both the medium- and high-nicotine conditions in the second; a significant linear trend was observed for number of sensations as a function of plasma nicotine level in the second study. For the high-nicotine cigarette, 19 of 22 subjects experienced at least one sensation (mean around three), starting around 2.5 min after lighting up. Together, these studies support the existence of a dose-response relationship for nicotine-induced euphoric sensations; suggest that they are more pronounced following overnight abstinence than following minimal deprivation, and in more dependent smokers; and characterize in detail the temporal features of these sensations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46338/1/213_2005_Article_BF02247422.pd

Discordance of physiological and biochemical response to smoking and to psychological stress

Both smoking and psychological stress produce marked effects upon cardiovascular function, and several studies have demonstrated that in combination they produce additive or potentiating effects. More recently, it has been reported that individuals strongly reactive to psychological stress are also strongly reactive to nicotine. In an attempt to replicate and extend those findings, we examined reactivity to smoking and competitive mental arithmetic across several physiological and biochemical variables. Despite stable responding across mental arithmetic trials, we were unable to demonstrate significant correlations between reactivity to smoking and to a psychological stressor. We further observed that anxiety level, when low, was a poor predictor of desire to smoke and of withdrawal, whereas higher anxiety levels were more tightly linked to these measures. These findings have implications for the iDentification of individuals at risk of cardiovascular disease as well as for the design of smoking treatment and relapse prevention programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72030/1/j.1360-0443.1990.tb01607.x.pd

Temporal stability and within-subject consistency of nicotine withdrawal symptoms

This study tested the temporal stability and within-subject consistency of the Diagnostic and Statistical Manual-III-R (DSM-III-R) nicotine withdrawal symptoms in 39 (21 female, 18 male) regular smokers. Subjects provided withdrawal symptom ratings while smoking ad libitum and during two 48-hour abstinence periods that were separated by 1 week. All but two symptoms, increased eating and hunger, demonstrated adequate temporal stability (i.e., stability coefficients >= .70). Within-subject consistency was found for impatience, anxiety, difficulty concentrating, and irritability. The total (average) score emerged as the most stable and consistent indicator of withdrawal. Results of a cluster analysis suggest the presence of two groups of smokers based on the withdrawal experience. Possible reasons for variability in nicotine withdrawal symptom reports are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31078/1/0000755.pd

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46446/1/213_2004_Article_BF00518198.pd

Effects of nicotine abstinence and menstrual phase on task performance

Both menstrual phase and nicotine have been shown to affect task performance. Though conflicting results have been reported, at least one well-controlled study has demonstrated that women at midluteal phase show superior performance on speech articulation and speeded motor coordination tests, but poorer performance on perceptual-spatial tests, than during menses. Smokers have demonstrated superior performance on numerous tasks following nicotine than following placebo. To explore the separate and combined influence of these factors, we studied 13 regularly-menstruating smokers using a two (smoking vs. 12 hours' abstinence) by two (menstrual vs. midluteal phase) factorial design. During each session, subjects completed a test battery including two speeded motor coordination tasks, a computerized reaction time test, and the Stroop (1935) color/word test. Subjects completed the Stroop color and color-word tasks significantly faster after ad lib smoking than after overnight abstinence. No other significant differences emerged. Our findings replicate, in an all-female sample, previous reports that speed of cognitive processing is reduced by nicotine abstinence (or enhanced by nicotine administration). Our failure to observe menstrual cycle effects raises the possibility that the anti-estrogenic effects of smoking may attenuate phase differences in performance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31479/1/0000401.pd

Cotinine in an ultrafiltrate of saliva

Background. We have developed a device for the simplified collection of a prepurified sample of saliva in the mouth.Method. The device is based on the principle of an osmotic pump and accumulates about 1.2 ml of an ultrafiltrate of saliva within 8 min. We have investigated the ultrafiltrate for its utility as a biological medium in the evaluation of cigarette smoking status.Results. (a) In 58 matched samples from 13 subjects, the correlation coefficient for the cotinine concentration in the saliva and the ultrafiltrate was 0.95; (b) in matched plasma and ultrafiltrate samples from 27 smokers, the correlation coefficient for the cotinine concentrations was 0.96 with plasma containing 1.2 times the ultrafiltrate mean; (c) in a nonsmoker, elevated cotinine levels could be detected in the ultrafiltrate more than 24 hr after smoking 2 cigarettes, and the pattern of rise and decrease reflected that in whole saliva; and (d) in a habitual smoker, the mean cotinine concentration in the ultrafiltrate was 157 ng/ml (SD +/- 25.7 ng/ml) during a period of smoking 15 cigarettes per day and dropped to a mean of 47 ng/ml (SD +/- 10.5) when smoking was reduced to 5 cigarettes per day; after cessation of smoking, detectable concentrations of cotinine persisted for up to 5 days.Conclusion. The device facilitated the aesthetic, noninvasive collection of a biological sample useful in the validation of smoking status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30282/1/0000684.pd

Sweet taste preference in women smokers: Comparison with nonsmokers and effects of menstrual phase and nicotine abstinence

Cigarette smokers weigh less than comparably aged nonsmokers, and many gain weight following cessation. Though some evidence suggests that nicotine reduces food intake, with a selective effect on sweet-tasting foods, the issue remains unresolved. In the current study, 64 women (20 smokers, 26 never-smokers, and 18 ex-smokers) were tested for sweet taste preference; 9 of these smokers were studied under conditions of both ad lib smoking and overnight abstinence, in three hormonally verified menstrual phases. 1) Although no overall differences were detected in taste preference among the three groups, significantly more smokers than nonsmokers preferred the higher sucrose concentrations. 2) No significant differences due to menstrual phase were observed. 3) Although preference ratings did not differ significantly between overnight abstinence and ad lib smoking, a subset of smokers who preferred higher sucrose concentrations rated their preference for the solutions significantly higher during the ad lib smoking sessions. Our findings suggest that smoking and nonsmoking women differ with respect to taste preference and that, at least in a subset of female smokers, preference is affected by nicotine abstinence/acute dosing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29019/1/0000049.pd