Tobacco smoking is a 'dependence', not a 'habit'.
Explore the source record for details and available documents.
Behavior, Addictive↗
Biomedical subjects
K A Perkins
Publications and source records attributed to K A Perkins.
Sex differences in nicotine effects and self-administration: review of human and animal evidence.
Although both the human and animal literatures are notable for the general lack of attention paid to possible sex differences in drug self-administration behavior, evidence is accumulating to suggest that males and females may differ in factors that maintain tobacco smoking or nicotine self-administration. Self-administration of nicotine per se may be less robust in women, and women are less sensitive than men to some effects of nicotine that may be reinforcing. Compared to men, smoking behavior of women may be influenced more by non-nicotine stimuli associated with smoking, suggesting greater conditioned reinforcement of smoking in women. Moreover, nicotine replacement, the current standard treatment for smoking cessation, is sometimes less effective in women, further suggesting the need for greater consideration of non-nicotine factors that may maintain women's smoking. Very recent research on rats also indicates sex differences in nicotine self-administration. However, these differences are complex and suggest that nicotine-seeking behavior is composed of several components, including hedonic, incentive-motivational, and conditioning effects; males and females may differ in one or more of these components. Menstrual or estrous cycle phase effects on the maintenance of nicotine self-administration are not particularly apparent in humans or animals, although cycle phase may influence other stages of dependence (e.g., withdrawal symptoms during cessation). Future research should evaluate further the consistency of results across human and non-human species, identify the conditions and procedures under which sex differences are observed, and elucidate the specific components of reinforcement that may differ between males and females. Studies also should examine the possible generalizability of these sex differences to other drugs of abuse. Identification of specific factors responsible for these sex differences may lead to improved interventions for smoking cessation and other substance abuse in women.
Animals↗
Nicotine self-administration.
Any research pertaining to smoking or nicotine must demonstrate that its findings relate to changes in smoking or nicotine self-administration in order to be potentially relevant to understanding nicotine dependence or to treating smoking cessation. Nicotine alone, isolated from tobacco smoke, is self-administered by animals and humans. Pharmacological factors such as speed of dosing, dose amount, and pre-treatment with nicotinic antagonists clearly influence onset or rate of nicotine self-administration. However, environmental cues associated with nicotine intake can also substantially influence rate of self-administration and must be considered in the development of any treatment for smoking cessation. The specific acute subjective and behavioral effects of nicotine responsible for maintaining self-administration need to be identified, along with the minimum nicotine dose necessary for these effects. Individual differences in these effects, such as between men and women, also need to be examined. Findings in neuroscience and other areas of research need to be directly related to nicotine self-administration in order to clearly understand how they influence nicotine dependence. Overlooked by researchers is the influence of environmental factors, including social facilitation, on smoking or nicotine self-administration; these factors must be the primary cause of smoking relapse that occurs more than a week or so after a quit attempt. Laboratory-based findings must be extended to the natural environment to determine the degree to which they relate to smoking and nicotine reinforcement among smokers in the community (the population and venue for future treatment efforts).
Animals↗
Fluoxetine versus placebo to decrease the smoking of depressed alcoholic patients.
Explore the source record for details and available documents.
Adult↗
Baseline-dependency of nicotine effects: a review.
'Rate-dependency', a founding observation of behavioral pharmacology, generally indicates that effects of drugs will be inversely related to the rate of operant responding under control conditions (i.e. decrease in high-rate behaviors and increase in low-rate behaviors). 'Baseline-dependency' encompasses rate-dependency and extends this notion to other drug effects, including those assessed by means other than 'rate' (such as subjective mood self-reports). Although little human research has specifically investigated the effects of nicotine as a function of baseline level of responding, a number of studies suggest baseline-dependent differences in the influence of nicotine on behavioral and cognitive task performance and on subjective mood responses. Results of many animal studies also are very consistent with these observations. Baseline-dependency, perhaps, is most clearly demonstrated in comparisons between groups selected on the basis of specific characteristics (e.g. high vs low 'trait hostility'), or within subjects as a result of acute environmental manipulations (e.g. high vs low 'stress' task). Moreover, baseline-dependency of the effects of nicotine may have broader applicability in explaining individual differences in vulnerability to nicotine dependence, particularly among those with psychiatric disorders (e.g. depression). While individual differences in responses to nicotine may be due to differences in pharmacological sensitivity to nicotine, as commonly assumed, they also may be due partly to individual and situationally determined differences in baseline level of responding on the measure of interest. Consideration of the conditions under which baseline-dependent effects of nicotine are observed may clarify both individual difference and situational influences on responses to nicotine.
Affect↗
Interaction of stress, smoking, and dietary restraint in women.
Smoking cessation often results in weight gain but certain subtypes of smokers may be more likely than others to gain weight. Women high in dietary restraint ("restrainers") increase food intake and gain more weight than nonrestrainers during smoking cessation. Restrainers have also been reported to increase food intake following laboratory stressors. Therefore, the present study was designed to measure the influence of stress on food intake and subjective distress during acute smoking abstinence in restrained and nonrestrained women. Participants were 48 women, 18-40 years old, comprising six groups (n = 8 per group) in a 2 x 3 x 2 design. Groups consisted of two levels of restraint (restrained and nonrestrained) and three levels of smoking (ad lib. smokers, abstinent smokers, and nonsmokers), whereas the within-participant manipulation involved two sessions differing in stress (stress and control). Snack foods were available for consumption. Results showed that distress, measured by the Stress-Arousal Checklist and visual analogue measures of tension and anxiety, was higher in the stress session for all groups except for restrainers who smoked ad lib. Furthermore, distress was significantly higher in smoke-abstinent restrainers during the stress session than all other conditions. However, despite differences in distress, no effect was observed for food intake. Desire for a cigarette showed a sharper increase over the stress session for restrainers compared with nonrestrainers but did not differ in the control session. These data suggest that restrainers may use smoking to reduce distress and may increase smoking, but not eating, during stress.
Adolescent↗
The role of corticosteroids in nicotine's physiological and behavioral effects.
This paper reviews evidence indicating that adrenal corticosteroids modulate the responsiveness of mice and rats to nicotine. Adrenalectomy increases, and both acute and chronic corticosteroid administration decrease, some of the physiological and behavioral effects of nicotine. One function of adrenal steroids may be to regulate stress-induced changes in nicotine sensitivity. Another is to mediate the development of chronic tolerance when nicotine is given intermittently, and when the resulting tolerance has a learned component. A role of glucocorticoids in the development of tolerance to nicotine is suggested by the findings that a conditioned elevation of plasma corticosterone, which anticipates nicotine delivery, accompanies the development of chronic tolerance and that environmental cues evoke a conditioned corticosterone response, but only after they have become associated with nicotine delivery. The mechanisms by which adrenal steroids modulate nicotine sensitivity are not known, although recent in vitro evidence suggests that steroids can rapidly and reversibly reduce nicotinic receptor function. While most of the data are consistent with the hypothesis that corticosteroids reduce nicotine responsiveness, and thus promote a learned form of tolerance, there are new findings that corticosteroids increase the development of sensitization to the locomotor-activating effects of nicotine. These data suggest that formulations postulating a unidirectional effect of corticosteroids on nicotine's actions (e.g. decreased sensitivity) must be revised to take into account interacting variables such as the specific nicotine effect being studied and whether that effect normally exhibits tolerance or sensitization. Finally, research is presented which indicates that the corticosterone-elevating effects of nicotine, previously reported for experimenter-administered drug, are also produced when nicotine administration is contingent on an operant response, and at a dose which sustains the development of nicotine self-administration in rats. These findings highlight the feasibility of using self-administration models in future explorations of the relationship between adrenal steroids and nicotine function.
Adrenal Cortex Hormones↗
Importance of environmental distractors in the effects of nicotine on short-term memory.
This study examined the role of environmental context in mediating the effects of nicotine on short-term memory performance (i.e., working memory). Male and female smokers (n = 12, overnight tobacco abstinent) and nonsmokers (n = 11) were administered nicotine (20 ug/kg) and a placebo (0 ug/kg) by means of a measured-dose nasal spray procedure on separate days. Participants were tested on a variant of S. Sternberg's (1966) memory search task. Half of the memory task sets involved the presentation of an auditory environmental distraction. Improvements in short-term memory performance with nicotine were primarily seen in smokers and in the presence of the distracting stimuli. These results suggest that environmental conditions, such as the presence of a distracting stimulus, may play an important role in mediating the effects of nicotine.
Adult↗
Nicotine discrimination and self-administration in humans as a function of smoking status.
Nicotine's discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 micrograms/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 micrograms/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 micrograms/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 micrograms/kg nicotine from placebo (> or = 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 micrograms/kg on the quantitative task and at 12 micrograms/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of "head rush", which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use.
Adult↗
Acute reinforcing effects of low-dose nicotine nasal spray in humans.
Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers.
Administration, Inhalation↗
Influence of acute smoking exposure on the subsequent reinforcing value of smoking.
The reinforcing value of smoking (i.e., the degree to which a smoker will work to obtain smoking) after varying the magnitude of prior smoke exposure in smokers not trying to quit was examined. Eight men and 8 women participated in 5 sessions involving manipulation of prior exposure to smoking: 0, 2, 6, or 12 puffs after overnight smoking abstinence or ad-lib smoking before the session. After exposure, participants engaged in a computer task involving concurrent schedules of reinforcement for smoke puffs (16% all trials) versus money (4-64%). Only the greatest amount of prior exposure (ad lib) produced a significant reduction in subsequent responding for smoke puffs. No exposure condition significantly increased responding above that for 0 puffs, indicating no priming effect. By contrast, self-report measures of desire to smoke and amount of money participants would pay for a cigarette declined sharply with greater prior exposure. These measures were correlated only weakly with smoke-reinforced responding on the behavioral task, suggesting that subjective versus behavioral measures assess different dimensions of smoking's reward value.
Adult↗
Membership of tobacco industry scientists in scientific societies.
Explore the source record for details and available documents.
Conflict of Interest↗
Influence of training dose on nicotine discrimination in humans.
Non-human research indicates that drug discrimination results may depend largely on the specific training conditions, including initial training dose. It has recently been shown that humans can discriminate among different doses of nicotine delivered by nasal spray. In this study, we examined the influence of training dose on subsequent behavioral discrimination of a range of nicotine doses. Male (n = 17) and female smokers (n = 16) were randomly assigned to "low" (10 micrograms/kg) versus "high" (30 micrograms/kg) nicotine training dose groups and trained reliably to discriminate this dose from placebo (0) on day 1 (> or = 80% correct identification). All but six subjects (four in low, two in high) learned this discrimination and continued on to day 2, in which both groups received 0, 5, 10, 20, and 30 micrograms/kg in ascending order (30 min between dosings) and were tested for generalization with their training dose using quantal and quantitative behavioral discrimination tasks. Subjective responses via traditional self-report measures were also assessed. Nicotine-appropriate responding on day 2 was significantly greater in low- versus high-dose groups, especially at 5 micrograms/kg. However, this difference due to training dose was seen more in women than in men. Discrimination behavior was associated with subjective effects of head rush in males, and with head rush and decline in urge to smoke in females. These results show that discriminative stimulus effects of nicotine are not fixed properties of the drug, but can be influenced by training conditions, and that effects associated with this discrimination may differ between men and women.
Adult↗
Acute thermogenic effects of nicotine and alcohol in healthy male and female smokers.
Nicotine intake is associated with lower body weight in both women and men. Despite its energy content, alcohol consumption is also associated with lower body weight in women but not in men. Each drug may reduce weight by acutely increasing thermogenesis. During four sessions, nicotine (20 micrograms/kg per dosing) or placebo was given to male and female smokers (n = 9 each) via measured-dose nasal spray every 30 min for 2 h after consumption of diet tonic water with or without alcohol (0.5 g/kg). Each nicotine/placebo dosing was followed by assessment of energy expenditure by indirect calorimetry. Alcohol alone induced no significant effect in men or women, whereas nicotine alone and combined with alcohol induced a significant thermogenic effect in men but not women. These results are consistent with other research suggesting a reduced thermogenic responsiveness to drugs in women and indicate that nicotine must act via appetite suppression to reduce body weight in women. Similarly, these findings do not support the notion that alcohol is inversely related to body weight in women because of excessive acute thermogenesis.
Adult↗
Nicotine preference in smokers as a function of smoking abstinence.
Overnight smoking abstinence increases desire to smoke and intensity of smoking behavior in smokers, but it is not completely clear that this reflects an increase in reinforcement from the psychoactive effects of nicotine per se. We examined choice of nicotine vs. placebo via nasal spray (Study 1) and nicotine vs. nonnicotine cigarette puffs (Study 2) in separate groups of smokers during each of two sessions, following overnight abstinence vs. no abstinence. In each study, subjects followed a forced choice procedure in which they were instructed to self-administer six sprays/puffs from between the two nasal sprays/cigarettes every 15 min for 2 h following initial exposure to each. In Study 1, choice of nicotine spray (1.5 micrograms/kg per spray) increased significantly following abstinence vs. no abstinence (47 +/- 6% vs. 34 +/- 5%, respectively, p < 0.05). This shift in choice was more pronounced in the subset of smokers (choosers, n = 9 out of 24) who selected nicotine on more than 50% of choices on the abstinent day. Choosers exhibited greater responses to initial nicotine exposure on positive (e.g., pleasant, vigor) but not aversive (e.g., jittery, uneasy) subjective measures, suggesting that greater positive reinforcement from nicotine per se predicted subsequent choice. In Study 2, abstinence similarly increased choice of nicotine vs. nonnicotine cigarette puffs (82 +/- 6% vs. 64 +/- 8%, p < 0.05), although nearly all subjects (12 of 13) preferred the nicotine cigarette following abstinence. These results indicate that choice of nicotine per se, isolated from tobacco smoke, increases significantly after overnight tobacco abstinence.
Adult↗
Society for Research on Nicotine and Tobacco.
The proceedings of the inaugural scientific meeting of the Society for Research on Nicotine and Tobacco (SRNT) are summarized. The primary objective of the meeting was to foster the exchange of information on the effects of nicotine and tobacco use, as well as factors which influence their use, drawing from biological, behavioral and social sciences. Much of this research can be viewed as a tale of "two" drugs--nicotine as a key to an important public health problem, and nicotine as a classical tool of physiological and pharmacological research. A historical overview of research on "both" drugs is provided first. Public policy alternatives for reducing the prevalence of tobacco use have been derived in part from basic and clinical research results and are briefly outlined. Evidence for genetic determinants on nicotine use and effects is presented using data from twin studies and from molecular genetic research with humans and animals. Consistent with this research, there is evidence of individual differences in pharmacokinetics and effects of nicotine, which could account for differences in smoking behavior and nicotine dependence. Finally, recent developments in the therapeutic uses of nicotine and novel nicotinic agonists with schizophrenia, Alzheimer's disease, Parkinson's disease, Tourette's syndrome and ulcerative colitis are presented. Overall, the research presented at the meeting demonstrated the vast diversity of areas of study involving nicotine and tobacco, as well as the rich opportunities for cross-communication among researchers from different disciplines.
Animals↗
Individual variability in responses to nicotine.
Individual variability in acute responses to nicotine, which may be defined as variable magnitude of effects following controlled dosing, is generally attributed to stable characteristics of tobacco users such as genetic/constitutional factors or to chronic behavioral factors (e.g., long-term use of other drugs). Often overlooked, however, is that such variability may also be due to the transient influence of the situational factors in which people consume nicotine, such as acute stress or physical activity. Results of selected studies from the author's laboratory provide examples of each of these sources of variability in nicotine responding on subjective, behavioral, and physiological measures. All studies used a nasal spray method of nicotine dosing or controlled smoking (paced puffing) to control acute nicotine exposure, an essential methodological feature of any research on individual differences in acute responses to nicotine. As an example of genetic/constitutional factors, gender differences in nicotine responding have begun to receive some attention, with few differences emerging. However, females may be more responsive than males to nonnicotine stimuli associated with smoking (e.g., sight and taste of smoke). In terms of chronic behavioral factors, long-term use of nicotine produces attenuation of most subjective and some behavioral effects of nicotine, reflecting chronic tolerance, and the possibility that chronic use of other drugs may alter responses to nicotine (i.e., cross-tolerance or cross-sensitization) deserves greater study. Of particular emphasis in this review is the modulating influence of acute situational factors on nicotine responding. Human studies have shown that magnitude of nicotine's subjective effects may depend on the predrug subjective state, level of physical activity vs. rest, and concurrent acute intake of other drugs, among other situational factors. Proper consideration of these situational factors may reveal the greatest source of individual variability in responding to nicotine and clarify the impact of more stable genetic/constitutional or chronic environmental factors.
Arousal↗
Acute tolerance to nicotine in smokers: lack of dissipation within 2 hours.
Greater understanding of development and dissipation of acute tolerance to nicotine may help explain temporal patterns of nicotine self-administration in smokers. The time course of dissipation of acute tolerance to nicotine was examined in 16 smokers (8M, 8F) participating in four sessions differing on pretreatment exposure or time interval prior to nicotine (20 micrograms/kg) challenge: placebo 30 min before, or nicotine (20 micrograms/kg) 30, 60, or 120 min before challenge. Nicotine and placebo were administered by measured-dose nasal spray. The measurement battery consisted of subjective, cardiovascular, thermal pain detection, and behavioral performance measures. Results demonstrated significant acute tolerance (i.e. smaller responses to nicotine challenge following nicotine versus placebo pretreatment) for most subjective measures and for heart rate. Acute tolerance dissipated with lengthening inter-dose interval for two subjective measures, dose strength and arousal, but there was no tolerance dissipation for other measures. In contrast, nicotine pretreatment resulted in acute sensitization of finger temperature (vasoconstriction) response, which dissipated with lengthening interval. No acute tolerance was observed for thermal pain detection or performance measures. These findings demonstrate that acute tolerance develops quickly to some subjective and cardiovascular effects of nicotine. However, acute tolerance to most effects did not dissipate over 2 h, suggesting that, following acute tolerance development during initial exposure, most smokers generally obtain similar magnitude of effects from each subsequent nicotine exposure (i.e. cigarettes smoked later in the day).
Adult↗