Effects Of Nicotine In Humans Research Articles

The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis.

Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans. Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots. Sixteen eligible articles, including k = 5 studies of pain tolerance (n = 210), k = 5 studies of pain threshold (n = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges' g = 0.28, 95% CI = 0-0.55, Z = 1.99, p = 0.05) and pain tolerance (Hedges' g = 0.32, 95% CI = 0.05-0.59, Z = 2.30, p = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of -0.37 (95% CI = -0.77 to 0.03, Z = -1.80) but with no statistical significance (p = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges' g = 0.37, 95% CI = 0.29-0.64, Z = 5.33, p < 0.01). These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

This review of research on behavioral discrimination of nicotine and how it informs public health policy for reducing risk of tobacco dependence is adapted from Kenneth A. Perkins's American Psychological Association Division 28 (Psychopharmacology and Substance Abuse) 2020 Med Associates Brady/Schuster Award Lecture. The author's initial programmatic clinical research on nicotine is introduced, especially efforts to develop and validate a novel method of acute nicotine dosing. After the public health rationale for characterizing the discriminative stimulus effects of nicotine in humans are described, details from two separate programs of research on nicotine discrimination in humans are presented. The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine's neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects. The second, more recent program focused on threshold doses for discrimination of nicotine by cigarette smoking, a program that was very difficult to do until the past decade, and how nicotine's self-reported "reward" and preference via choice behavior relate to its discriminability. Differences due to menthol and degree of tobacco dependence were also examined. For each of these two programs, the main findings of selected studies are noted, followed by very recent work on nicotine discrimination and choice that informs Food and Drug Administration's efforts to formulate public policy to improve health and reduce the nearly half million American deaths per year due to persistent tobacco use. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impact of delivery rate on the acute response to intravenous nicotine: A human laboratory study with implications for regulatory science.

Faster delivery rate enhances the abuse potential of drugs of abuse, yet systematic studies on the impact of delivery rate on the acute effects of nicotine in humans are lacking. Using an intravenous (IV) nicotine infusion procedure that allows precise control of rate of delivery, we examined the impact of nicotine delivery rate on the positive subjective drug effects, smoking urges, withdrawal, heart rate, blood pressure and attention function in smokers. Twenty-four male and female (ages 21-35) dependent smokers attended five experimental sessions, following overnight abstinence from smoking. Using a crossover design, participants attended five sessions, where they were assigned to a random sequence of saline infusion or 1mg nicotine delivered over 1, 2.5, 5 or 10min at rates of 1, 0.4, 0.2 or 0.1mg/min, respectively. The positive subjective effects of nicotine were most robust under the two faster delivery rate conditions, 1- and 0.4-mg nicotine/min. In contrast, all nicotine delivery rates were equally more effective than saline in alleviating urges to smoke. Likewise, nicotine-induced heart rate increases did not vary with the rate of nicotine delivery. Lastly, the cognitive enhancing effects of nicotine were observed only under the two slowest delivery rate conditions-0.1- and 0.2-mg nicotine/min. Collectively, these findings support the critical role of delivery rate in optimizing nicotine's abuse potential versus potential therapeutic effects and have timely implications for developing novel therapeutics for nicotine dependence, as well as for tobacco regulatory science.

E-cigarette Awareness among Young Adults: A Pilot Survey Study.

ObjectivesThis study sought to assess: 1) pervasiveness of vaping or electronic cigarette (e-cigarette) use, 2) General understanding of information on vaping or e-cigarette use, 3) Prevalence and respondent awareness of smoking/vaping prevention programs, and 4) Awareness of the harmful effects of e-cigarettes.MethodsThis was a cross-sectional survey of 101 young adults (ages 18-24) in the United States designed to assess the prevalence and knowledge of vaping. Ten questions tested this knowledge and prevalence, some directly (for example, "Which of the following have you used? Select all that apply") and some indirectly (Which of the following pictures corresponds with that of an e-cigarette?). After the results were obtained, the crosstabs showed the percentage of respondents who identified a particular answer for each question.ResultsMost of the surveyants had heard about e-cigarettes (about 88.6% of all respondents). About 55% of the study’s sample attended schools with tobacco prevention programs. Sixty-four percent of the cohort thought that vaping is actually safer than traditional cigarettes. Most (87.4%) of the people were able to identify an e-cigarette when shown a picture of e-cigarettes versus two computer flash-drives and a cigarette. However, 78.2% of respondents were aware of at least one of the effects of nicotine in humans, which corresponds with the number of respondents who were familiar with any of the provided e-cigarette brands (as 71.7% of respondents to question six knew of the six provided brands of e-cigarettes) and the respondents with parents who smoke (as about 75% of respondents said that neither parent smokes). Thirty-eight percent of respondents had used either traditional tobacco products (such as cigarettes, cigars, or chewing tobacco) or e-cigarettes before, with 13% of respondents having used both tobacco and e-cigarettes.

A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans.

Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene cluster in risk for heavy smoking and several smoking-related disorders. The heavy smoking risk allele might reduce the aversive effects of nicotine, but this hypothesis has not been tested in humans. We evaluated the effects of a candidate causal variant in CHRNA5, rs16969968, on the acute response to nicotine in European American (EA) and African American (AA) smokers (n=192; 50% AA; 73% male). Following overnight abstinence from nicotine, participants completed a protocol that included an intravenous (IV) dose of saline and two escalating IV doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine, withdrawal severity, and cognitive performance before and after the nicotine administration session. The heavy smoking risk allele (rs16969968*A; frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive effects (P<5 × 10(-8)) with marked specificity. This effect was evident in EA and AA subjects analyzed as separate groups and was most robust at the highest nicotine dose. Rs16969968*A was also associated with greater improvement on a measure of cognitive control (Stroop Task) following nicotine administration. These findings support differential aversive response to nicotine as one likely mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking.

The Reinforcing Effects of Nicotine in Humans and Nonhuman Primates: A Review of Intravenous Self-Administration Evidence and Future Directions for Research.

Cigarette smoking is largely driven by the reinforcing properties of nicotine. Intravenous (IV) self-administration procedures are the gold standard for investigating the reinforcing effects of psychoactive drugs. The goal of this review was to examine the results of published investigations of the reinforcing effects of nicotine measured using IV self-administration procedures in humans and nonhuman primates. The body of literature using nonhuman primate subjects indicates nicotine functions as a positive reinforcer when available for self-administration via IV catheters. However, it can also be difficult to establish IV nicotine self-administration in nonhuman primates and sometimes supplemental strategies have been required (e.g., priming injections or food deprivation) before subjects acquire the behavior. Although the body of literature using human subjects is limited, the evidence indicates nicotine functions as a reinforcer via the IV route of administration in adult cigarette smokers. Rates of nicotine self-injection can be variable across subjects and responding is sometimes inconsistent across sessions in both humans and nonhuman primates. The Family Smoking Prevention and Tobacco Control Act, enacted in 2009, gave the Food and Drug Administration regulatory authority over the manufacture, marketing, and distribution of tobacco products. Research examining the threshold reinforcing doses for initiation and maintenance of nicotine self-administration, comparisons of the reinforcing effects of nicotine in adolescent versus adult subjects, investigations of gender differences in the reinforcing effects of nicotine, and studies of the abuse liability of non-nicotine tobacco product constituents and their ability to alter the reinforcing effects of nicotine will inform potential tobacco regulatory actions.

A Single 4 mg Dose of Nicotine Decreases Heart Rate Variability in Healthy Nonsmokers: Implications for Smoking Cessation Programs

The vast majority of work on the physiological effects of nicotine in humans has been done in smokers or smokers trying to quit. Such studies can be confounded by tolerance, desensitization of receptors, or withdrawal. Because of these difficulties, there is still some dispute as to whether nicotine is proparasympathetic or prosympathetic in humans. To circumvent these difficulties, we assessed the effect of nicotine on autonomic function by measuring changes in heart rate variability (HRV) in nicotine-naive healthy subjects. Twenty males and 20 females aged between 18 and 25 years received 4 mg oral nicotine lozenge or placebo. HRV was assessed in 15-min periods before, during, and after ingestion. There were no significant changes in any measure after placebo administration. During and after nicotine ingestion, heart rate increased to 78 ± 2 beats per minute (bpm) from a baseline level of 75 ± 2 bpm (p < .01). Nicotine significantly increased low frequency (LF; normalized units) from 66 ± 2 at baseline to 70 ± 2 at 15-30 min postingestion (p < .01) and decreased high frequency (HF; normalized units) from 28 ± 2 to 24 ± 1 (p < .01). LF/HF ratio was therefore substantially increased from 2.9 ± 0.3 to 3.7 ± 0.3 (p < .01). A single dose of 4 mg oral nicotine produces a significant reduction in HRV (i.e., a proportional decrease in high-frequency variability) in healthy young nonsmokers consistent with a reduced vagal activity. This has implications for nicotine replacement treatments aimed at cessation of smoking.

Lack of reinforcement enhancing effects of nicotine in non-dependent smokers

Recent animal research has shown that, aside from its primary and secondary reinforcing effects, nicotine may enhance reinforcement from stimuli unrelated to nicotine intake. Little human research has directly examined this potentially important influence of nicotine. We report two virtually identical studies examining the influence of nicotine, via nasal spray (study 1) and cigarettes (study 2), on the reinforcing effects of rewards unrelated to nicotine intake. Both studies involved young adults with some past smoking exposure but no history of nicotine dependence. Reinforcement was assessed by responses on a simple operant computer task reinforced by: money, music, the termination of aversive noise, or no reward (control). Participants responded for rewards on three separate sessions, involving intermittent dosing of 0, 5, or 10 microg/kg nicotine via nasal spray (study 1) or the smoking of 0.05 or 0.6 mg nicotine cigarettes or no smoking (study 2). Results showed no effects of nicotine, by nasal spray or cigarette smoking, on reinforced responses, although nicotine increased some subjective responses (e.g. head rush/buzzed, liking). Nicotine via smoking also did not influence affect or hedonic ratings of slides varying in mood valence in an exploratory trial in study 2. These results do not support the notion that nicotine per se enhances the reinforcing value of other reinforcers in humans. Any reinforcement enhancing effects of nicotine in humans may be specific to dependent smokers or may be relatively narrow and dependent upon procedural conditions different from those in the current studies.

The discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine as a function of light physical activity

Smokers often experience the acute effects of cigarette smoking while they are engaged in the light physical activity of routine tasks. However, virtually all laboratory-based research on these effects is conducted under conditions of quiet rest and, thus, may not generalize to effects in the natural environment. We examined changes in the discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine in humans as a function of the level of concurrent physical activity. Men and women smokers (N = 17) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) at rest. Three sessions then followed, in which the generalization of discrimination was tested across a range of doses (0-20 microg/kg) while at rest or engaged in very light or light physical activity (15% and 30% of heart rate reserve, respectively) via bicycle ergometer. Generalization testing involved both two- and three-choice ("novel" option) quantitative procedures. Self-reported mood via the Profile of Mood States and visual analog scales, and cardiovascular measures of heart rate and blood pressure were obtained concurrent with discrimination responding. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure under the same rest or activity conditions. Results showed that physical activity did not significantly alter nicotine discrimination or reinforcement, as no interactions between activity and nicotine were observed. When activity and nicotine influenced the same subjective and cardiovascular responses, they acted in a generally additive fashion. These findings suggest that research on the acute effects of nicotine conducted under typical resting laboratory conditions generally are not altered by light physical activity and so may generalize to the effects of nicotine under conditions common in the natural environment.

Lack of startle modulation by smoking cues in smokers

The startle reflex methodology has been used to study the effects of nicotine in humans and the motivational effects of smoking cues in smokers. However, no other studies investigate startle modulation by smoking cues in smokers compared to non-smokers. In the other studies, smoking deprivation was manipulated in smokers or smokers were not compared directly to non-smokers. The goal of this study was to examine the temporal course of information processing following the presentation of a smoking-related cue using the startle probe methodology in smokers compared to non-smokers. Thirty-four smokers were selected on the basis of nicotinic dependence according to the DSM-IV, and compared to 34 non-smokers. During testing, subjects viewed neutral pictures and smoking related pictures displayed on a computer screen. Acoustic startle stimuli were delivered at various times after picture onset (60, 120 or 5000 ms) to examine inhibition by lead stimulus and the affective modulation of startle. The magnitude of startle reflex inhibition increased in smokers compared to non-smokers, at 60 and 120 ms. In all, there was no PicturexGroup interaction effect. We showed that smoking cues have no impact on the startle reflex of either group, even if, in line with previous results, prepulse inhibition was higher in smokers than non-smokers. These results suggest that smoking cues have no effect on the positive reinforcement of nicotine consumption, and that cognitive factors play a primary role in the development and maintenance of tobacco dependence.

Cognitive effects of nicotine in humans: an fMRI study

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric “n-back” task in healthy nonsmoking males after the administration of nicotine (12 μg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy ( P = 0.008) in all active conditions (2%–11%), and had a load-specific effect on latency ( P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task ( P < 0.05, corrected at the voxel level), nicotine produced an increased response ( P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest ( P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.

Nicotine: a review of its role in atherosclerosis.

Overwhelming evidence is available associating cigarette smoking and several pathologic conditions, including cardiopulmonary disease and malignancies (Table 1). In the United States, one in six deaths is related to tobacco smoking. Extensive research has been done over the past few decades aimed at understanding the pathophysiology of tobacco-related disease and elucidating the mechanisms by which tobacco smoke causes disease. The Framingham study is the best-known prospective investigation that established the risk factors for coronary heart disease and peripheral vascular disease. Five factors were shown to be predictors of atherosclerosis: hypertension, serum cholesterol level above 297 mg/ 100mL, glucose intolerance, left ventricular hypertrophy on electrocardiography, and smoking. Of these factors smoking history was the most predictive of the development of intermittent claudication. Cigarette smoking especially accelerates atherosclerosis in the coronary arteries, the aorta, the carotid and cerebral arteries, and the large arteries in the peripheral circulation. Smoking is associated with an increased risk of acute cardiovascular events, including acute myocardial infarction, sudden death, and stroke. Other effects include aggravation of stable angina pectoris, intermittent claudication and vasospastic angina, rethrombosis after thrombolysis, and restenosis after angioplasty. Cigarette smoke is a complex mixture of more than 4,000 chemical constituents distributed in particulate and gaseous phases. The most important constituents includenicotine,aromatichydrocarbons, sterolsandoxygenated isoprenoid compounds, aldehydes, nitriles, cyclic ethers, and sulfur compounds (Table 2). PHARMACOLOGY AND METABOLISM Nicotine is a tertiary amine composed of a pyridine and a pyrrolidine ring (Table 3). Tobacco contains both a levorotatory S-nicotine and an R-isomer in quantities up to 10% of the total nicotine present. Nicotine is a weak base with a pKa of 8.0. At a physiologic pH, approximately 30% of nicotine is nonionized and can readily cross cell membranes. Nicotine binds stereospecifically to acetylcholine receptors at the autonomic junctions and the brain. Nicotine cholinergic receptors have been detected in the brain, autonomic ganglia, and the neuromuscular junction. The diversity of nicotinic cholinergic receptors may explain the varied effects of nicotine in humans. Nicotine is distilled from burning tobacco, carried proximally, and deposited in the small airways and alveoli. On inhalation, nicotine is rapidly absorbed from cigarette smoke, from which it enters the arterial circulation and is rapidly distributed to body tissues. It takes 10 to 20 seconds for nicotine to pass through the brain. Nicotine levels than fall, owing to uptake by peripheral tissues and later to elimination of nicotine from the body. Arteriovenous differences during cigarette smoking are substantial, with arterial levels exceeding venous levels 6to 10-fold. The rapid delivery of nicotine results in an intense pharmacologic response, owing both to higher arterial levels entering the brain and effects occurring rapidly, before there is adequate time for the development of tolerance. Nicotine plasma concentrations in smokers range between 10 mol/L and 10 mol/L.22 The elimination half-life of nicotine during the use of tobacco or nicotine products averages 2 to 3 hours. Nicotine levels accumulate over 6 to 8 hours during regular smoking. But there is a very long terminal half-life, 20 hours or more, reflecting the slow release of nicotine from body tissues. Nicotine crosses the placenta freely and has been found in amniotic fluid and the umbilical cord blood of neonates. Nicotine is metabolized extensively, primarily by the liver, but also to a lesser extent by the lung (Fig. 1). The No competing interests declared.

Membership of tobacco industry scientists in scientific societies1

AddictionVolume 92, Issue 5 p. 517-520 Free Access Membership of tobacco industry scientists in scientific societies† Kenneth A. Perkins, Kenneth A. Perkins Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USASearch for more papers by this author Kenneth A. Perkins, Kenneth A. Perkins Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USASearch for more papers by this author First published: 24 January 2006 https://doi.org/10.1080/09652149737782Citations: 5 † The author has received several grants from the National Institute on Drug Abuse for research on the effects of nicotine in humans. The views stated here reflect the author's personal opinion and are not necessarily official policy of the author's employer, source of funding, or any scientific societies to which he may belong. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume92, Issue5May 1997Pages 517-520 ReferencesRelatedInformation

Nicotine Replacement Therapy During Pregnancy-Reply

In Reply. —Drs Seidman and Stevenson suggest that nicotine may be a teratogen and that providing a potentially toxic drug to pregnant women raises significant medical and ethical questions. There is no question that nicotine is a potentially toxic drug and even a teratogen. The critical issues in deciding to administer a potentially toxic drug to a patient include the likelihood of toxic effects in the doses and dosing regimens to be administered and the potential benefits vs risks of the therapy. Studies demonstrating direct toxic effects of nicotine in animals generally have used doses of nicotine higher than those consumed by tobacco users or delivered by nicotine replacement therapies. The relevance of animal toxicity studies to the understanding of the toxic effects of nicotine in humans is therefore still uncertain. On the other hand, we know without question that tobacco smoking during pregnancy may be highly injurious to the

Chapter 28 Subjective and behavioural effects of nicotine in humans: some sources of individual variation

Despite its addictiveness, the subjective effects of nicotine in "smoking doses" are of low intensity compared with those of other addictive drugs. Although mildly pleasurable to many regular users, it causes no striking euphoriant effects and its effects on mood, performance and the level of arousal are relatively small. This chapter does not attempt to list or review the numerous effects of nicotine, but focuses instead on some of the multiple sources of individual variation. The subjective and behavioral effects of nicotine in humans differ markedly, not only between individuals but also within individuals, according to the stage of their smoking career, their level of dependence and the time since their last few doses. Some of the influences and mechanisms discussed include innate and acquired factors, pharmacokinetic factors, acute and chronic tolerance, learning and conditioning. It is not clear to what extent the effects of nicotine are primary, or how much they reflect reversal or relief of acquired withdrawal effects. Only one study has found a "rebound" element in the effects of withdrawal and although chronic exposure to nicotine induces an increase in the number of nicotinic receptors, chronic tolerance to nicotine has not been demonstrated in humans. Acute tolerance (tachyphylaxis) develops rapidly to many of the effects of nicotine and is completely reversible after nicotine depletion. Other effects of nicotine are less sensitive to acute tolerance. It is suggested that it is the effects of nicotine at postsynaptic receptors that are most susceptible to acute tolerance and that those mediated by its action at presynaptic receptors are less sensitive to it. Due to accumulation of nicotine and other pharmacokinetic factors, for most of the day and much of the night, regular smokers have high levels of acute tolerance to nicotine. In other words, there is a chronic partial blockade of its agonist effects at postsynaptic receptors. This explains why nicotinic receptors are upregulated rather than downregulated and why heavy smokers experience no subjective effects from a cigarette smoked during the course of a normal smoking day. When the effects of acute tolerance are unmasked after abstinence for 24 h, it is the more addicted heavy smokers who experienced more severe withdrawal effects who also have stronger subjective and heart rate effects following the first post-abstinence cigarette. Their greater sensitivity to nicotine after abstinence may reflect their higher density of unoccupied nicotinic receptors. On the other hand, those who have higher innate sensitivity may be more likely to take up smoking and to become more dependent if they

Environmental Determinants of the Reinforcing Effects of Nicotine in Humans

Experimental studies indicate instructions (told received nicotine > told received placebo) and drug history (exsmokers > never-smokers) increase the degree to which the stimulus effects of nicotine will serve as a reinforcer in humans. Cross-study comparisons and correlational data suggest schedule (concurrent > single access to nicotine and placebo), duration of exposure (longer > shorter exposure), and setting (therapeutic > experimental settings) also increase the reinforcing effect of nicotine. Empirical study of when and how environmental factors control the reinforcing effects of nicotine is crucial to specifying multicausal models of tobacco dependence.

Reinforcing effects of nicotine in humans and experimental animals responding under intermittent schedules of i.v. drug injection.

The self-administration paradigm is an experimental model of drug dependence in which the reinforcing properties of drugs can be directly assessed. This paradigm avoids the possible confounding influence of nonpharmacologic factors which may contribute to drug taking in the nonlaboratory environment. When animals serve as subjects, social and cultural factors unique to humans may also be eliminated as confounding influences. Most drugs of abuse are self-administered by animals and humans under such conditions. Until 1981, laboratory studies of nicotine self-administration suggested that nicotine, in its own right, was only a marginally effective reinforcer. As will be shown in the present review, a study by Goldberg and his co-workers in 1981 [13] demonstrated clearly that nicotine could serve as a highly efficacious reinforcer in laboratory animals. There are several parameters which can function to substantially strengthen the behavior which leads to nicotine ingestion. These include the following: (1) intermittent availability of nicotine, (2) intermittent presentation of nicotine-paired stimuli, and (3) concurrent schedules of food reinforcement. Initial findings from a human IV nicotine self-administration study were consistent with those from the animal studies. Together these results confirm that nicotine can function to control behavior by serving as a reinforcer for animals and humans. The results also suggest that commonly used tobacco products function as ideal nicotine delivery systems for controlling behavior since they provide discrete nicotine-paired stimuli and lend themselves to intermittent nicotine delivery.