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The thermogenic effects of nicotine and caffeine during physical activity compared with rest were examined in male and female smokers (n = 10 each). During eight sessions, nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaffeinated coffee with or without added caffeine (5 mg/kg), followed by assessment of energy expenditure by indirect calorimetry while subjects engaged in standardized, low-intensity cycle ergometer riding (activity) or remained at quiet rest. Results indicated significant thermogenic effects of nicotine and caffeine individually, with the combination of nicotine and caffeine producing additive effects. Expenditure attributable to nicotine, caffeine, or their combination was significantly enhanced during activity compared with rest, but only for males and not females. Plasma nicotine concentrations were influenced by activity and caffeine, but these pharmacokinetic changes did not appear to explain the differences in expenditure. These findings suggest a sex difference in thermogenic effects of nicotine and caffeine during casual physical activity and potentially explain some of the apparent individual variability in expenditure due to tobacco smoking.

Understanding tolerance to effects of nicotine in humans may elucidate processes involved in the onset and maintenance of tobacco dependence. Subjective, behavioral and cardiovascular responses to nicotine were examined as a function of past history of nicotine exposure (i.e., smokers vs. nonsmokers, chronic tolerance) and of immediately preceding nicotine exposure (acute tolerance). Dose-effect relationships between nicotine (0-2 micrograms/kg via measured-dose nasal spray) and each response were determined in male and female smokers (n = 17) and nonsmokers (n = 18), with different doses presented on different days. Each day, subjects also received a challenge dose of 20 micrograms/kg 30 min after the previous dosing to assess acute tolerance. Plasma nicotine concentrations were 30% lower in nonsmokers compared with smokers and analyses were adjusted to control for this difference. Results showed significant changes in nearly all responses as a function of nicotine dose. Dose-effect curves were shifted to the right or dampened in smokers relative to nonsmokers for most subjective and some behavioral responses, consistent with chronic tolerance, but there was less evidence of chronic tolerance to other behavioral effects or to cardiovascular responses. A pattern of acute tolerance generally similar to that of chronic tolerance was observed across response domains (i.e., clear acute tolerance to subjective measures but less to behavioral or cardiovascular effects). These results support the notions that regular use of nicotine is associated with chronic functional tolerance and that repeated nicotine exposure during a single episode produces acute tolerance. A similar pattern of chronic vs. acute tolerance suggests similarity of mechanisms responsible for both "types" of tolerance. However, variability in tolerance magnitude across subjective, behavioral and cardiovascular response domains indicates that different mechanisms may be responsible for these different effects of nicotine.

Tolerance to subjective effects of nicotine may induce novice smokers to increase the magnitude and frequency of their nicotine self-dosing. In this study, smokers (n = 8) and nonsmokers (n = 7) participated in three sessions involving presentation of 0, 7.5, or 15 micrograms/kg nicotine 30 min for 2 h via measured-dose nasal spray, with different doses presented on separate days. Subjective responses were assessed using visual analog scales (VASs) of jittery, light-headed, relaxed, dizzy, and head rush, and the Profile of Mood States (POMS) scales of vigor, confusion, fatigue, tension, and the composite scale of arousal. Smaller responses in smokers vs. nonsmokers were viewed as evidence for chronic tolerance. In addition, on each day subjects received a fifth, challenge dose of 30 micrograms/kg 30 min after the previous dosing. Smaller responses to the challenge dose as a function of increasing prior nicotine dosing during Trials 1-4 were viewed as evidence for acute tolerance. Results showed significant changes in most measures as a function of nicotine dose, and the dose-response curves for most VAS and POMS scales tended to be shifted to the right, or dampened, in smokers relative to nonsmokers, consistent with chronic tolerance. However, smokers and nonsmokers tended to respond to nicotine in opposite directions for POMS scales of vigor and arousal, perhaps reflecting withdrawal relief in smokers. Acute tolerance on a few selected VAS and POMS scales was apparent for both smokers and nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

We tested whether the inverse relationship between smoking and body weight may be due in part to nicotine's acute effects on reducing hunger and eating. On four mornings, male and female smokers (n = 10 each), abstinent overnight from smoking and food, received one of three nicotine doses (7.5, 15, and 30 micrograms/kg) or placebo (0) via nasal spray every 30 min for 2 h. Self-reported hunger and satiety ("fullness") and craving for cigarettes were obtained after each dose presentation. Subjects subsequently ate ad lib from a large array of food items varying in sweet taste and fat content. For both males and females, nicotine had no effect on self-reported hunger, but cigarette craving was decreased. Rather than being decreased, caloric intake during the meal was unexpectedly increased following nicotine compared with placebo. Cigarette craving increased after the meal, and this increase was unaffected by nicotine dose. There were virtually no differences between males and females in any effects of nicotine. These results indicate that nicotine may not acutely suppress appetite in fasting smokers and suggest that other actions of nicotine or smoking may account for the lower body weights of smokers.

The acute thermogenic effect of nicotine was examined in cigarette smokers under conditions of rest and two levels of low-intensity physical activity comparable to that normally engaged in by sedentary adults. Male and female smokers (n = 10 each) each received 0 (placebo), 7.5, 15, or 30 micrograms/kg nicotine via measured-dose nasal spray once every 30 min for 90 min, with each dose presented on a separate occasion. After each dose presentation, subjects engaged in 10 min of rest or low-intensity activity at 30 or 60 watts (W) using a bicycle ergometer. For males, results indicated that expenditure attributable to nicotine was more than twice as large during 60-W activity compared with rest, while that during 30-W activity was intermediate. For females, expenditure attributable to nicotine was generally similar to that of males during rest and 30-W activity but was significantly lower during 60-W activity, indicating an apparent "inverted-U" relationship with activity intensity. The enhanced effect of nicotine was specific to energy expenditure, since heart rate showed dose-dependent changes that were generally similar regardless of activity level. These findings confirm a mediating influence of physical activity level on the acute metabolic effect of nicotine, especially in males, and may have implications for explaining individual differences in body weight changes due to tobacco smoking and cessation.

The inverse relationship between smoking and body weight may be due in part to nicotine's effects on reducing hunger and eating. Male smokers and nonsmokers (n = 10 each), abstinent overnight from smoking and food, participated in four sessions, involving consumption of a liquid caloric load or water followed by nicotine (15 micrograms/kg) or placebo via nasal spray every 20 min for 2 h. Hunger and satiety ("fullness") ratings were obtained prior to each dose presentation. At the end of the two sessions involving the caloric load (simulating breakfast), subjects were also presented with typical lunch/snack food items varying in sweet taste and fat content for ad lib consumption. Results indicated that, for both smokers and nonsmokers, the hunger-reducing effects of nicotine occurred only following caloric load consumption, and there was no effect of nicotine on hunger afer water consumption. Smokers unexpectedly reported greater satiation than nonsmokers following the caloric load regardless of nicotine or placebo condition. Nicotine also resulted in less caloric intake during the meal, and the decrease was not specific to consumption of sweet, high-fat foods. These results indicate that nicotine reduces appetite, possibly helping to explain the influence of smoking on body weight.

Performance on finger-tapping and handsteadiness, tasks opposite in response requirements, was compared between male smokers and nonsmokers (n = 10 each) on two occasions, once following intake of nicotine (15 micrograms/kg) by measured-dose nasal spray and once following placebo. Compared with nonsmokers, smokers had significantly greater increase in finger-tapping speed due to nicotine. On the other hand, smokers tended to have improved performance on handsteadiness (i.e., less involuntary movement) due to nicotine, while nonsmokers had impaired performance, although this difference was not significant. Nicotine-induced changes in performance on each task were inversely related, suggesting specificity of the behavioral effects of nicotine depending on task demands, rather than a generalized effect. These effects of nicotine on behavioral performance may be important in understanding the reinforcing value of nicotine intake, and differences in effects as a function of smoking history may suggest chronic adaptation to nicotine.

The thermogenic effect of nicotine intake after calorie consumption was investigated to determine if nicotine influences metabolic response to a calorie challenge. Smokers and nonsmokers (10 males in each group), matched for body weight, age, and physical fitness, each participated in four sessions that involved consuming a liquid calorie load (4.77 kcal/kg body wt) or water, followed by nicotine (15 micrograms/kg body wt) or placebo via nasal spray every 20 min for 2 h. Energy expenditure was significantly increased above baseline resting metabolic rate (RMR) over the 2 h by nicotine alone (6.5% of RMR, p less than 0.01). However, the combined effect of nicotine after calorie load (20.1% of RMR, p less than 0.001) was not significantly greater than the effect of calorie load alone (18.4% of RMR, p less than 0.001). Smokers and nonsmokers did not differ in baseline RMR or in response to nicotine or calorie load. These results confirm the thermogenic effect of nicotine but suggest that the effect of nicotine after calorie consumption is less than additive.

1. In two separate studies using healthy male smokers as subjects, the acute cardiovascular effects of a measured dose of nicotine (15 micrograms/kg) were examined in conjunction with light physical activity and following consumption of a meal, conditions typical of nicotine intake via smoking. 2. Increases in heart rate and systolic blood pressure attributable to nicotine were similar during rest, physical activity, and following eating, demonstrating additivity with the cardiovascular effects of activity and a caloric load. Diastolic blood pressure was less affected by nicotine. 3. These results indicate that cardiovascular activity is acutely increased following nicotine (smoking) regardless of other influences on the cardiovascular system. Such effects may help explain increased risks of acute cardiac abnormalities due to smoking.

Nicotine's effects on reducing perception and/or hedonics of sweet and fat taste may lead to less intake of sweet tasting, high-fat foods by smokers, helping to explain their generally lower body weights. Smokers and nonsmokers (n = 10 males each) rated perception (intensity and sensitivity) and hedonics (liking) of sweet/fat taste in milk samples varying both in sucrose (0, 5, 10, 20% w/w) and fat (0.1, 3.5, 11.7, 37.6% w/w) concentration on two occasions, once following intermittent presentation of nicotine (15 micrograms/kg) via measured dose nasal spray and the other following placebo. Nicotine significantly reduced perceived intensity of fat but not sweet taste and had no effect on sensitivity to either taste. There was no effect of nicotine on hedonics of sweet/fat taste. On the other hand, although there were no differences between smokers and nonsmokers in perception of sweet or fat, hedonics of sweet/fat taste was reduced in smokers regardless of nicotine or placebo intake. Thus, nicotine may acutely decrease fat taste perception without influencing sweet/fat hedonics, while long-term exposure (i.e., being a smoker) may produce chronically decreased taste hedonics without altering perception.

Rationale: Nicotine consumption in both human and animal studies has been strongly associated with changes in feeding-related behaviors and metabolism. The current dogma is that nicotine is an anorexic agent that decreases food intake and increases metabolism, leading to decreased body weight gain. However, there are conflicting reports about the acute effects of nicotine on hunger in humans. No study has reported nicotine-induced decreases in food intake within minutes of consumption, suggesting that our understanding of the pharmacological effects of nicotine on appetite and feeding may be incorrect., Objectives: The aim of this study was to elucidate effects of acute nicotine intake on feeding and drinking behavior., Methods: Adult male Wistar rats were trained to intravenously self-administer nicotine. Microstructural and macrostructural behavioral analyses were employed to look at changes in food and water intake at different timescales., Results: At the macrostructural level (hours to days), nicotine decreased body weight gain, decreased feeding, and was associated with increases in feeding and body weight gain during abstinence. At the microstructural level (seconds to minutes), nicotine increased feeding and drinking behavior during the first 5 min after nicotine self-administration. This effect was also observed in animals that passively received nicotine, but the effect was not observed in animals that self-administered saline or passively received saline., Conclusions: These results challenge the notion that the initial pharmacological effect of nicotine is anorexigenic and paradoxically suggest that an acute increase in food intake minutes after exposure to nicotine may contribute to the long-term anorexigenic effects of nicotine., (© 2022. The Author(s).)

Rationale: Cd81 -/- (knockout) mice have previously been reported to have reduced cocaine preference and increased striatal dopamine content and dopamine turnover, but normal learning and memory in the Morris water maze. The effects of Cd81 on other behaviors and drugs of abuse have not been investigated., Objectives and Methods: We measured the effects of Cd81 -/- in a modified two-bottle choice test for nicotine, as well as in somatic signs of nicotine withdrawal, four tests of affective behavior, and tyrosine hydroxylase gene expression assays., Results: We found that Cd81 loss-of-function significantly increased voluntary nicotine consumption and somatic signs of nicotine withdrawal. Nicotine consumption of Cd81 -/- female mice increased for 3 weeks and then remained relatively stable for the next 5 weeks, suggesting that their nicotine consumption continued to be limited by aversion to higher nicotine doses. Cd81 -/- also produced a dramatic and significant increase in struggling in the forced swim test and a significant increase in the time spent in the light chamber of the light/dark box. The elevated plus maze and the tail suspension test did not show a main effect of genotype. Therefore, we conclude that Cd81 did not have an overall effect on anxiety- or depression-like behavior. Tyrosine hydroxylase mRNA levels were unchanged., Conclusions: Cd81 knockouts have a strongly increased nicotine preference, plus a proactive response to specific stressful situations. Together with reports of increased striatal dopamine content and anecdotal reports of increased aggressiveness, these provide intriguing parallels to some aspects of post-traumatic stress disorder., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tolerance to the effects of nicotine reflects physiological adaptation and may be related to the development and persistence of smoking behavior. However, little is known about tolerance to nicotine in humans, in part due to methodological difficulties. This study examined chronic and acute tolerance to nicotine's effect on heart rate (HR) using a measured-dose nasal spray nicotine procedure. Eight "Light" smokers (less than 20 cigarettes per day) and ten "Heavy" smokers (greater than or equal to 20 per day) participated in two sessions on separate days in which they received four administrations (1 every 20 min) of a high nicotine dose (15 micrograms per kg body weight, equivalent to a typical cigarette) or a low nicotine dose (7.5 micrograms/kg) while HR was monitored during the 5 min following each administration. Compared with Light smokers, Heavy smokers had significantly smaller HR responses to the high dose, indicating greater chronic tolerance, but there was no difference between groups in response to the low dose. Acute tolerance to HR response across the four 5-min periods was not observed with either dose. However, subsequent examination of HR response in the first 2 min following each dose administration did suggest acute tolerance, particularly for the low dose, as this more acute HR response declined from the first to the last administration. These results demonstrate chronic and, to a lesser extent, acute tolerance to HR effects of nicotine and suggest that both may be dose dependent.

The acute effects of nicotine on resting metabolic rate (RMR) were examined to identify a mechanism that may help explain the inverse association between smoking and body weight. Multiple administrations of two nicotine doses (moderate [15 micrograms/kg body wt] and low [7.5 micrograms/kg body wt]) and a placebo (0 micrograms) were presented to 18 male smokers via nasal-spray solution on three separate occasions while RMR was assessed by computerized open-circuit indirect calorimetry. Plasma nicotine levels confirmed the reliability of dosing. RMR increases of 6% above base line after both moderate and low doses were significantly greater than the 3% increase after the placebo. Subsequent examination of the effects of smoking a nonnicotine cigarette suggested that the small placebo effect was due to acute metabolic consequences of inhalation. These results confirm that intake of nicotine, isolated from tobacco smoke, significantly increases RMR in humans. However, the results also indicate that non-pharmacological, behavioral aspects of smoking may also contribute to acutely increasing RMR in smokers.

The metabolic effects of nicotine have been implicated in the relation between smoking and lower body weight. This study examined whether the nicotine-induced increase in the metabolic rate observed at rest is also present during physical activity. We compared the energy expenditure of 10 male smokers receiving nicotine (15 micrograms per kilogram of body weight) with that of 10 male smokers receiving placebo on two occasions, each including a period of rest and a period of exercise on a modified bicycle ergometer at workloads designed to simulate and standardize light daily activity. All had abstained from cigarette smoking the night before the study. The excess energy expenditure attributable to nicotine was more than twice as great during exercise (difference between groups, 0.51 kJ per kilogram per hour, or 12.1 percent of the metabolic rate at rest; P less than 0.001) than during rest (0.23 kJ per kilogram per hour, or 5.3 percent of the metabolic rate at rest; P less than 0.05). In contrast, the expenditure was not affected by placebo during exercise or rest in the smokers or in a comparison group of 10 non-smokers, indicating that smoking status has no long-term metabolic effect in the absence of short-term nicotine intake. We conclude that the relatively small metabolic effect of nicotine when the subject is at rest is enhanced during light exercise. Our data also suggest that the weight gain that often follows smoking cessation may be influenced not only by nicotine intake but also by the level of physical activity a smoker typically engages in while smoking.

To determine whether using nicotine exacerbates exertional heat strain through an increased metabolic heat production (Hprod) or decreased skin blood flow (SkBF), 10 nicotine-naïve trained males [37 ± 12 yr; peak oxygen consumption (V̇ o 2peak): 66 ± 10 mL·min−1·kg−1] completed four trials at 20°C and 30°C following overnight transdermal nicotine (7 mg·24 h−1) and placebo use in a crossover, double-blind design. They cycled for 60 min (55% V̇ o 2peak) followed by a time trial (∼75% V̇ o 2peak) during which measures of gastrointestinal (Tgi) and mean weighted skin ( T ¯ sk) temperatures, SkBF, Hprod, and mean arterial pressure (MAP) were made. The difference in ΔTgi between nicotine and placebo trials was greater during 30°C (0.4 ± 0.5°C) than 20°C (0.1 ± 0.7°C), with T ¯ sk higher during nicotine than placebo trials (0.5 ± 0.5°C, P = 0.02). SkBF became progressively lower during nicotine than placebo trials (P = 0.01) and progressively higher during 30°C than 20°C trials (P < 0.01); MAP increased from baseline (P < 0.01) and remained elevated in all trials. The difference in Hprod between 30°C and 20°C trials was lower during nicotine than placebo (P = 0.01) and became progressively higher during 30°C than 20°C trials with exercise duration (P = 0.03). Mean power output during the time trial was lower during 30°C than 20°C trials (24 ± 25 W, P = 0.02), and although no effect of nicotine was observed (P > 0.59), two participants (20%) were unable to complete their 30°C nicotine trials as one reached the ethical limit for Tgi (40.0°C), whereas the other withdrew due to "nausea and chills" (Tgi = 39.7°C). These results demonstrate that nicotine use increases thermal strain and risk of exertional heat exhaustion by reducing SkBF. NEW & NOTEWORTHY: In naïve participants, acute nicotine use exerts a hyperthermic effect that increases the risk of heat exhaustion during exertional heat strain, which is driven by a blunted skin blood flow response. This has implications for 1) populations that face exertional heat strain and demonstrate high nicotine use (e.g., athletes and military, 25%–50%) and 2) study design whereby screening and exclusion for nicotine use or standardization of prior use (e.g., overnight abstinence) is encouraged. [ABSTRACT FROM AUTHOR]

Rationale: Previous neuroimaging studies of cognition involving nicotinic acetylcholine receptor (nAChR) agonist administration have repeatedly found enhanced task-induced deactivation of regions of the default mode network (DMN), a group of brain systems that is more active at rest and mediates task-independent thought processes. This effect may be related to pro-cognitive nAChR agonist effects Objectives: The present study sought to test whether nAChR modulation of the DMN is bi-directional, i.e., whether a nAChR antagonist would reduce task-induced deactivation. Methods: Eighteen healthy non-smokers underwent functional magnetic resonance imaging while performing a letter N-back task. Scans were performed after nicotine administration (7 mg/24 h, transdermally), after administration of the nAChR antagonist mecamylamine (7.5 mg, p.o.), and after double placebo, in counterbalanced sequence. Blood-oxygen-level-dependent (BOLD) signal was analyzed within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC) regions of interest—central hubs of the DMN in which consistent nAChR agonist–induced changes had previously been identified. Results: Nicotine enhanced hit rate in both the 0-back and 2-back condition, while mecamylamine slowed reaction time in the 2-back condition. Mecamylamine reduced task-induced deactivation of vmPFC and PCC. Nicotine had no significant effects on the BOLD signal. Conclusions: The finding that nAChR tone reduction by mecamylamine weakened task-induced DMN deactivation indicates that a constant tone of nAChR activation helps regulate DMN activity in healthy individuals. This suggests that low nAChR tone may play a causal role in DMN dysregulation seen in conditions such as mild cognitive impairment or Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Nicotine use amongst athletes is high and increasing, especially in team sports. This narrative review examines the rationale behind its use and evidence of its effect on physical performance, and considers important factors that should determine future research efforts. To date, ten studies have assessed muscular strength and power, sub- or maximal endurance and high-intensity exercise when nicotine (medication) or smokeless tobacco was used as an intervention. Two studies observed an ergogenic effect, one an ergolytic with the remaining seven reporting no change. These studies have notable limitations and confounding factors that include participant tolerance to nicotine, interindividual responses, the nicotine delivery system used and failure to adhere to rigorous experimental/scientific design. Further research is encouraged to address these limitations and determine the extent to which anti-doping and governing bodies should consider promoting, coordinating and monitoring any effort against nicotine and nicotine-containing substances in sports. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to determine sex/gender differences in smoke exposure and to quantify the role of potential predictors including puffing behaviors, nicotine dependence, and non-nicotinic factors. Methods: The Pennsylvania Adult Smoking Study (PASS) of 332 adult cigarette smokers utilized portable handheld topography devices to capture the smokers' profiles in a naturalistic environment. Sex/gender differences in salivary biomarkers were modeled using ANCOVA to account for measures of dependence (Fagerstrom Test for Nicotine Dependence, nicotine metabolite ratio [3-hydroxycotinine/cotinine]), and nondependence covariates including anthropomorphic factors and stress. The Blinder-Oaxaca method was used to decompose the sex/gender differences in nicotine uptake due to covariates. Results: Men had significantly higher cotinine levels (313.5 ng/mL vs. 255.8 ng/mL, p < 0.01), cotinine +3-hydroxycotinine levels, (0.0787 mol/L vs. 0.0675 mol/L, p = 0.01), puff volumes (52.95 mL vs. 44.77 mL, p < 0.01), and a lower nicotine metabolite ratio (0.396 vs. 0.475, p = 0.01) than women. The mean Fagerström Test for Nicotine Dependence score did not differ between men and women ( p = 0.24). Women had a higher mean Hooked on Tobacco Checklist score than men (7.64 vs. 6.87, p < 0.01). In multivariate analysis, nicotine metabolite levels were not significantly different by sex. Decomposition results show that ten predictors can explain 83% of the sex/gender differences in cotinine uptake. Height was the greatest contributor to these differences, followed by average puff volume. Conclusion and Impact: The higher levels of nicotine metabolites in men, compared to women, can be explained by height, weight, puff volume, and nicotine metabolism. [ABSTRACT FROM AUTHOR]

Background: Smoking has a thermogenic effect and is associated with low physical performance. Nevertheless, a direct, quantitative effect of acute smoking on exercise heat tolerance has not been reported. Methods: Sixteen healthy young male volunteers, eight cigarette smokers, and eight non-smokers participated in the study. All subjects performed a maximal oxygen consumption test (VO2max) and a standardized heat tolerance test (HTT) after at least 12 h without smoking under the following conditions: no nicotine exposure, 10 min after nicotine exposure (2 mg nicotine lozenge), and 10 min after smoking two cigarettes (0.8 mg nicotine in each cigarette, smokers only). Results: There was no significant effect of nicotine exposure on physiological performance and heat tolerance in the non-smokers group. In the smokers group, cigarette smoking, but not nicotine ingestion, resulted with higher heart rate (by 9 ± 9 bpm) at the end of the HTT (p < 0.05). Moreover, both smoking and nicotine ingestion increased smokers’ rectal temperature at the end of the HTT (by 0.24 ± 0.16 °C and 0.21 ± 0.26 °C, respectively, p < 0.05) and were associated with higher sweat rate during the HTT (by 0.08 ± 0.07 g/h and 0.06 ± 0.08 g/h, respectively, p < 0.05). Heart rate variability (HRV) analysis also revealed a higher LF/HF (low frequency/high frequency) ratio after exposure to nicotine and smoking in the smokers group compared with no exposure (2.13 ± 2.57 and 2.48 ± 2.76, respectively, p < 0.05), indicating a higher sympathetic tone. Conclusions: According to this preliminary study, cigarette smoking and nicotine ingestion increase the physiological strain during a HTT in smokers. Acute smoking may, therefore, increase heat intolerance and the risk to heat injuries. [ABSTRACT FROM AUTHOR]

Nicotine in tobacco smoke causes not only pathophysiological changes in the smoker's body, but also develops tolerance to its own action with repeated use. Repeated exposure to nicotine develops neuroadaptation of the receptors, resulting in tolerance to many of the effects of nicotine. Pharmacotherapies for smoking cessation should reduce withdrawal symptoms and block the reinforcing effects of nicotine without causing excessive adverse effects. All forms of nicotine replacement therapy (NRT) - gum, patches and inhaler - and bupropion are safe and effective for increasing smoking cessation rates in the short and long-term use. Combination NRT (more than one therapy) may be indicated in patients who have failed monotherapy. [ABSTRACT FROM AUTHOR]

This study was to investigate the effect of nicotine on insulin sensitivity and explore the underlying mechanisms. Treatment of Sprague-Dawley rats with nicotine (3 mg/kg/day) for 6 weeks reduced 43% body weight gain and 65% blood insulin level, but had no effect on blood glucose level. Both insulin tolerance test and glucose tolerance test demonstrated that nicotine treatment enhanced insulin sensitivity. Pretreatment of rats with hexamethonium (20 mg/kg/day) to antagonize peripheral nicotinic receptors except for α7 nicotinic acetylcholine receptor (α7-nAChR) had no effect on the insulin sensitizing effect of nicotine. However, the insulin sensitizing effect but not the bodyweight reducing effect of nicotine was abrogated in α7-nAChR knockout mice. Further, chronic treatment with PNU-282987 (0.53 mg/kg/day), a selective α7- nAChR agonist, significantly enhanced insulin sensitivity without apparently modifying bodyweight not only in normal mice but also in AMP-activated kinase-α2 knockout mice, an animal model of insulin resistance with no sign of inflammation. Moreover, PNU-282987 treatment enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in skeletal muscle, adipose tissue and liver in normal mice. PNU-282987 treatment also increased glucose uptake by 25% in C2C12 myotubes and this effect was total abrogated by STAT3 inhibitor, S3I-201. All together, these findings demonstrated that nicotine enhanced insulin sensitivity in animals with or without insulin resistance, at least in part via stimulating α7- nAChR-STAT3 pathway independent of inflammation. Our results contribute not only to the understanding of the pharmacological effects of nicotine, but also to the identifying of new therapeutic targets against insulin resistance. [ABSTRACT FROM AUTHOR]

Objective: In accordance with the pharmacist oath, service to the community is the moral responsibility of a clinical pharmacist. Patient counseling is one among the service to public towards greater wellbeing. It is designed to help people to explore and resolve their incongruity about behavior change. It was developed as a treatment for alcohol abuse, but it may also help smokers to a make a successful attempt to quit. The present study is aimed to study the role of clinical pharmacist in smoking cessation in smokers. Materials and Methods: A prospective randomized usual led trial was carried out. The study was approved by human institutional ethical committee. The sample size was calculated using standardized formula. Participants (n=80) were recruited based upon inclusion and exclusion criteria and were allocated on random basis into two groups, namely usual care and intervention care using computerized randomization model. Participants in both groups were counseled based on their nicotine dependence level. Results: We found improvements between baseline and after intervention regarding the outcome. At the end of motivational enhancement counseling, participants in the interventional arm showed significant improvement in quitting smoking habit than the usual arm. Conclusion: Study has proved that motivational enhancement counseling do have a tremendous reach in male smokers. The better understanding of the reason behind every individual smoker is an important key in motivating them and in getting the positive results. [ABSTRACT FROM AUTHOR]

The prevalence of cigarette and alcohol consumption is high among young adult males during the reproductive period. The current study aimed to evaluate the impact of concurrent chronic administration of nicotine and ethanol on the quality of sperm in the rat. Fifty healthy Wistar male rats were randomly divided into five groups ( n = 10) and were given the following for a period of 50 days: ethanol ( E), nicotine ( N), ethanol and nicotine ( E/ N); the control group ( C) and an intact ( I) group. Body weight as well as the weight, volume and dimensions of the testes and the weight of the cauda epididymidis and vas deference were measured. The concentration, motility, viability and membrane integrity of sperm were also assessed. There were no significant differences between body weight and all testis parameters including weight, volume and dimensions. The concentration and motility of sperm in the E/ N group was significantly reduced compared with the control group ( P < 0.01). Nevertheless, only a marginally significant decrease in sperm viability was found in the E/ N group compared with the control group. The study indicates that concurrent chronic administration of ethanol and nicotine may disturb male reproductive function. [ABSTRACT FROM AUTHOR]

We investigated the effects of short-term abstinence from smoking and acute nicotine administration on taste perception in smokers. We assessed sensitivity for salt and sucrose solutions and the self-reported intensity and pleasantness of these tastes, using a previously validated model of taste perception. This was in order to investigate mechanisms by which cigarette smoking and smoking cessation may modulate dietary behaviour. Male and female daily smokers attended a single testing session. Participants were randomised to either abstain for smoking for 12 h or smoke as usual on the morning of testing. At the testing session, participants completed subjective ratings of mood and ratings of intensity and pleasantness of salt and sucrose solutions, followed by measurement of the threshold at which these solutions could be detected on the tongue. Participants were then randomised to smoking either a nicotine-containing or denicotinised cigarette, after which they completed the same measures as previously. Our data suggest that following cigarette smoking, lower taste thresholds are obtained after smoking a denicotinised cigarette compared with a nicotinised cigarette, but among females only. This effect was not observed among males and did not differ as a function of abstinence condition. In addition, among non-abstinent smokers, females demonstrated higher taste thresholds (i.e. reduced sensitivity) for salt than males, but this sex difference was not observed among abstinent smokers. [ABSTRACT FROM PUBLISHER]

Attempts to simultaneously control food intake and smoking may lead to smoking cessation failure. We sought to model this relationship using a human laboratory paradigm of smoking lapse behavior. We examined the combined effect of food and nicotine deprivation, compared to nicotine deprivation alone, on the ability to resist smoking and on subsequent ad libitum smoking. In a between-subjects design, daily smokers ( N = 30) were all deprived of nicotine for 18 h and were either food-deprived (12 h) or not during a laboratory session. Following exposure to individualized food cues, participants had the option of initiating tobacco self-administration or delaying up to 50 min in exchange for monetary reinforcement. Subsequently, the tobacco self-administration period consisted of 1 h in which participants could choose to smoke or receive monetary reinforcement for cigarettes not smoked. Smokers who had been deprived of food and nicotine smoked their first cigarette sooner and were more likely to smoke at some point during the laboratory session, compared to those who were only nicotine-deprived. Those who were food- and nicotine-deprived smoked slightly more cigarettes than those who were nicotine-deprived only, although this difference was not statistically significant. There were no sex differences in outcomes. Hunger and food craving ratings while trying to resist smoking were greater in the food + nicotine-deprived group. Tobacco craving was predictive of outcome in both conditions. These findings support the hypothesis that food deprivation can undermine a smoker’s ability to resist smoking. [ABSTRACT FROM AUTHOR]

Empirical studies indicate that nicotine enhances some aspects of attention and cognition, suggesting a role in the maintenance of tobacco dependence. The purpose of this review was to update the literature since our previous review (Heishman et al. Exp Clin Psychopharmacol 2:345–395, ) and to determine which aspects of human performance were most sensitive to the effects of nicotine and smoking. We conducted a meta-analysis on the outcome measures of 41 double-blind, placebo-controlled laboratory studies published from 1994 to 2008. In all studies, nicotine was administered, and performance was assessed in healthy adult nonsmokers or smokers who were not tobacco-deprived or minimally deprived (≤2 h). There were sufficient effect size data to conduct meta-analyses on nine performance domains, including motor abilities, alerting and orienting attention, and episodic and working memory. We found significant positive effects of nicotine or smoking on six domains: fine motor, alerting attention-accuracy and response time (RT), orienting attention-RT, short-term episodic memory-accuracy, and working memory-RT (effect size range = 0.16 to 0.44). The significant effects of nicotine on motor abilities, attention, and memory likely represent true performance enhancement because they are not confounded by withdrawal relief. The beneficial cognitive effects of nicotine have implications for initiation of smoking and maintenance of tobacco dependence. [ABSTRACT FROM AUTHOR]

Alcohol has been shown to increase smoking urges and smoking behavior. However, alcohol’s effects on specific components of smoking behavior for nicotine versus non-nicotine factors and potential sex differences in this response have not been investigated. Forty-two young male and female non-dependent, heavy social drinking smokers participated in two double-blind laboratory sessions. They were randomized to either an alcohol (0.8 g/kg; n = 29) or placebo ( n = 13) beverage pre-administration group. After beverage consumption, they were assessed for smoking urges and then given the opportunity to smoke cigarettes which were either all nicotinized (0.6 mg/cigarette) or denicotinized (≤0.05 mg/cigarette) over a 3-h period; smoking behavior was quantified by a smoking topography device. Subjects took standardized puffs of the session’s cigarette both before and after beverage administration to provide a reference when making future smoking choices. Alcohol, compared with placebo beverage, increased both men’s and women’s smoking urge, as well as subjective ratings of smoking reference puffs for either nicotinized or denicotinized cigarettes. In terms of smoking choice behavior, regardless of cigarette type, alcohol (>placebo) increased men’s smoking behavior, including puff count, volume, and duration. In contrast, for women, smoking topography measures did not differ between alcohol and placebo conditions. In summary regardless of nicotine content, in men, alcohol increased smoking urge and behavior, whereas in women, alcohol increased smoking urge but did not increase smoking behavior. These results indicate that the mechanisms underlying co-use of alcohol and tobacco in women may be more complex than in men. [ABSTRACT FROM AUTHOR]

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 μg/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. [ABSTRACT FROM AUTHOR]

Opioid neurotransmission has been implicated in reinforcement-related processes for several drugs of abuse, including opiates, stimulants, and alcohol. However, less is known about its role in the motivational effects of nicotine and nicotine-associated environmental cues. This study investigated whether pretreatment with naltrexone, an opioid receptor antagonist, alters conditioned incentive salience of nicotine cues under two conditions: cue-induced reinstatement of nicotine-seeking after extinction and cue-maintained responding during extinction. The effect of naltrexone on nicotine self-administration during the maintenance phase was also examined. Male Sprague–Dawley rats were trained in daily 1-h sessions to self-administer nicotine (0.03 mg/kg/infusion, i.v.) on a fixed-ratio 5 schedule and associate a conditioned stimulus (CS) with each nicotine delivery. Once responding was extinguished by saline substitution for nicotine and omission of the CS, the reinstatement tests were conducted following subcutaneous administration of naltrexone (0, 0.25, 1, 2 mg/kg). In separate groups of rats, naltrexone (0, 2 mg/kg) was chronically given before each extinction sessions, where responses on the active lever resulted in presentations of the CS without nicotine infusion (saline substitution). Self-administration/naltrexone tests were conducted in different groups of rats receiving similar nicotine self-administration training. Naltrexone significantly attenuated the CS-reinstated responding on the active, previously nicotine-reinforced lever in the reinstatement tests and the CS-maintained active lever responding during the extinction tests. In contrast, neither acute nor chronic naltrexone produced an effect on nicotine self-administration behavior. These results indicate that activation of opioid receptors is implicated in mediation of the conditioned incentive properties of nicotine cues but not in the maintenance of nicotine self-administration. Therefore, these findings suggest that opioid receptor antagonists might have clinical potential for prevention of smoking relapse associated with exposure to environmental cues. [ABSTRACT FROM AUTHOR]

AbstractBackground:Nicotine exposure has been associated with weight loss and reduced weight gain. Previously, we have reported that nicotine exposure in rats is associated with reduced weight gain, unless diets are rigidly controlled. Leptin, a hormone released by adipose tissue, is believed to have appetite suppressant effects. We used a smokeless tobacco model to study leptin responses to nicotine or placebo treatment.Methods:We studied 6-week-old male and female Sprague-Dawley rats, and implanted 50 mg of nicotine or placebo pellets. Weight gain was controlled by chow restriction in all four groups of rats. Systolic blood pressure was measured noninvasively, and glucose, insulin, free fatty acid, and leptin responses to an oral glucose load were determined at 8.5 weeks of age.Results:Males were generally heavier than females, both before and after nicotine or placebo placement; there was no difference in weight between nicotine and placebo groups for each sex. Blood pressure was slightly, but not significantly, increased by nicotine treatment. Glucose, insulin, free fatty acid, and leptin responses to glucose were essentially unaffected by nicotine treatment.Conclusions:In summary, smokeless nicotine at this dose has no significant effect on fasting or postglucose leptin values in sexually immature male and female rats. [ABSTRACT FROM AUTHOR]

Impulsivity is related to greater risk of nicotine dependence, perhaps by enhancing sensitivity to nicotine’s reinforcing and rewarding effects during initial smoking experiences. We examined the influence of impulsivity characteristics on acute sensitivity to nicotine reward, reinforcement, and other effects in 131 young adult nonsmokers. Participants engaged in four sessions: the first three to assess dose–response effects of nasal spray nicotine (0, 5, 10 μg/kg) on reward, as well as mood, physiological, and performance effects, and the fourth to assess nicotine reinforcement using a choice procedure. Five impulsivity factors, derived from factor analysis of self-report (e.g., Barratt Impulsivity Scale, Sensation-Seeking Scale, Novelty seeking) and computer (stop–go, delay discounting, probability discounting) measures of impulsivity, were labeled “novelty seeking”, “response disinhibition”, “extraversion”, “inhibition”, and “probability/delay discounting”. The associations of novelty seeking with nicotine reinforcement and reward tended to move in opposite directions by sex, generally being directly related in men but inversely or unrelated in women. Similarly, response disinhibition was associated with reward and some mood responses to nicotine that differed by sex. Extraversion was inversely associated with nicotine reinforcement. Characteristics loading on to the other impulsivity factors had little association with nicotine sensitivity. These results are preliminary, but they suggest that characteristics broadly related to impulsivity, especially novelty seeking and response disinhibition, are associated with initial sensitivity to some effects of acute nicotine, including reinforcement and reward, and may do so differentially between men and women. [ABSTRACT FROM AUTHOR]

Discrete cues, such as drug-associated paraphernalia, play an important role in tobacco smoking and relapse, an effect that can be modelled in the nicotine-seeking behaviour of laboratory animals. However, the role of contextual stimuli (i.e. the drug taking environment) within nicotine dependence is less clear. The present study investigated the effects of contextual stimuli on nicotine detoxification and relapse. Male hooded Lister rats were trained to self-administer nicotine (0.03 mg/kg/infusion) in one of two distinct environmental contexts: transparent walls and rod floor or checkerboard walls and grid floor. Extinction of drug-seeking behaviour, either in the acquisition context or alternate context, was achieved by removing both nicotine infusions and response-contingent cues. The two contexts were then presented with or without nicotine priming and response-contingent cue presentation. The initial rate of extinction was quicker in a novel environment compared to in the same context as training, although similar low levels of responding were eventually reached. Nicotine priming and re-presentation of cues resulted in significant reinstatement of nicotine-seeking behaviour, but there was a trend towards a reduction in this effect when conducted in a novel environment. In addition, re-presentation of the acquisition context after extinction in the alternate context produced a significant reinstatement of nicotine-seeking behaviour without the need for nicotine priming and re-presentation of cues. Contextual stimuli are capable of modulating the extinction and reinstatement of nicotine-seeking behaviour, and exposure to environments previously associated with smoking may lead to an increased risk of relapse. Context is an additional factor that could be targeted when developing smoking cessation strategies. For example, the long-term success of cue exposure might be improved by conducting treatment in multiple settings. [ABSTRACT FROM AUTHOR]

Smoking one cigarette produces rapid nicotine dose-related increases in hypothalamic–pituitary–adrenal (HPA) axis hormones, mood, and heart rate, but relatively little is known about the effects of smoking several cigarettes successively. Twenty-four healthy adult men who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for nicotine dependence provided informed consent. After overnight abstinence from smoking, men smoked three low- or high-nicotine cigarettes for 4 min each at 60 min intervals. Samples for nicotine and hormone analysis, Visual Analog Scale (VAS) ratings of subjective effects and heart rate were collected at 4, 8, 12, 16, 20, 30, 40, and 50 min after each cigarette. After low-nicotine cigarettes, nicotine levels, adrenocorticotropin hormone, and heart rate did not increase significantly, cortisol and dehydroepiandrosterone decreased significantly, and positive VAS ratings were lower but parallel to ratings after high-nicotine cigarette smoking. After high-nicotine cigarettes, peak nicotine levels increased monotonically. HPA axis hormones increased after smoking, but peak levels did not differ significantly after successive high-nicotine cigarettes. Positive VAS ratings and heart rate increased after each high-nicotine cigarette, but peak levels were lower after smoking the second and third cigarette. ‘Craving’ decreased significantly after smoking both low- and high-nicotine cigarettes, then gradually increased during the 60 min interval between cigarettes. These data are consistent with clinical reports that the first cigarette after overnight nicotine abstinence is most salient. Tolerance to the subjective and cardiovascular effects of nicotine developed rapidly during repeated cigarette smoking, but nicotine-stimulated increases in HPA axis hormones did not change significantly.Neuropsychopharmacology (2008) 33, 749–760; doi:10.1038/sj.npp.1301455; published online 16 May 2007 [ABSTRACT FROM AUTHOR]

The motivational effects of nicotine-associated cues have been demonstrated in animal studies. However, it is unknown whether the effectiveness of nicotine cues in reinstating nicotine-seeking varies with the extent of prior nicotine self-administration. In addition, the issue of whether bupropion (an FDA-approved smoking cessation medication) interferes with the conditioned incentive of nicotine cues remains to be addressed. This study determined the relationship of cue-reinstated nicotine-seeking and the levels of prior self-administration and examined the effect of bupropion on cue-induced reinstatement of nicotine-seeking in comparison with that on self-administration. Male Sprague–Dawley rats were trained in daily 1-h sessions to intravenously self-administer nicotine at different doses (0, 0.015, 0.03, 0.06 mg/kg/infusion) and to associate an auditory/visual cue with each nicotine delivery. After extinction, three reinstatement tests at 15 day intervals were conducted with re-presentation of the cue without nicotine delivery. In separate groups of rats trained with 0.03 mg/kg/infusion nicotine, bupropion (0, 10, 20, 40 mg/kg) was intraperitoneally administered to different groups before the reinstatement and in a within-subject design before the self-administration tests. Cue-induced reinstatement of active lever responses was observed at all nicotine doses in the first reinstatement test, but at only the two highest doses during the second and third tests. The magnitude of reinstatement was positively correlated with level of prior responding for nicotine. Bupropion pretreatment decreased nicotine self-administration but enhanced cue-reinstated nicotine-seeking. These results demonstrate the positive correlation of cue-reinstated nicotine-seeking with prior responding for nicotine self-administration and the persistence of the cue effect after taking higher doses of nicotine. The results of pharmacological tests suggest that although it is able to help achieve smoking cessation, bupropion may have little clinical benefit for the prevention of relapse associated with exposure to environmental smoking cues. [ABSTRACT FROM AUTHOR]

Individuals vary in their susceptibility to nicotine addiction. However, there is little evidence that behavioral sensitivity to nicotine is dependent upon the functional state of nicotinic cholinergic receptors (nAChRs). This study aims to determine the relationship between in vivo behavioral desensitization and in vitro desensitization of nAChR function. Male Sprague–Dawley rats trained to discriminate nicotine were tested for development of acute behavioral tolerance. The rats were injected with nicotine (0.4 mg/kg free base, s.c.), tested for nicotine discrimination for 2 min, then injected with the same dose of nicotine 90, 180, and 270 min after the first injection and tested for nicotine discrimination after each injection. Susceptibility of nAChRs of individual rats to desensitization was assessed by use of the 86Rb+ efflux assay using synaptosomes prepared from the “thalamus,” which included the hypothalamus and midbrain as well as the thalamic nuclei. To desensitize nAChRs, synaptsosomes were superfused with low concentrations of nicotine (5, 10, 20, and 30 nM) before stimulation of 86Rb+ efflux with nicotine (10 μM). The slopes of the behavioral desensitization were plotted as a function of the decline of nicotine-stimulated 86Rb+ efflux after in vitro desensitization. A significant correlation was observed between the in vitro desensitization of thalamic 86Rb+ efflux and the extent of behavioral desensitization of individual rats. These findings are consistent with the idea that production of acute behavioral tolerance by nicotine is related to its ability to induce nAChR desensitization at the cellular level. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effects of nicotine on verbal working memory and the efficiency of the brain in processing verbal working memory. Subjects in the study were given nicotine patches, and it was found that while doing tasks that required verbal memory, nicotine had a negative effect on performance, and caused a loss of efficiency in the brain.

Nicotine is widely reported to increase alertness, improve co-ordination and enhance cognitive performance; however, to our knowledge there have been no attempts to replicate these findings in relation to exercise endurance. The purpose of this study was to determine the effects nicotine might have on cycling endurance, perception of exertion and a range of physiological variables. With local ethics committee approval and having obtained informed consent, 12 healthy, non-smoking men (22 ± 3 years; maximal O2 uptake, 56 ± 6 ml kg−1 min−1, mean ±s.d.) cycled to exhaustion at 18°C and 65% of their peak aerobic power, wearing either a 7 mg transdermal nicotine patch (NIC) or a colour-matched placebo (PLA) in a randomized cross-over design; water was available ad libitum. Subjects were exercising at approximately 75% of their maximal O2 uptake with no differences in cadence between trials. Ten out of 12 subjects cycled for longer with NIC administration, and this resulted in a significant 17 ± 7% improvement in performance ( P < 0.05). No differences were observed for perceived exertion, heart rate or ventilation. There were no differences in concentrations of plasma glucose, lactate or circulating fatty acids. In the absence of any effect on peripheral markers, we conclude that nicotine prolongs endurance by a central mechanism. Possible modes of action are suggested. [ABSTRACT FROM AUTHOR]

The article discusses research on the evidence of cellular nicotinic receptor desensitization in rats, exhibiting nicotine-induced acute tolerance. It examines the relationship between in vivo pharmacological desensitization and brain regional nicotinic cholinergic receptors function. It provides information on the methods and materials used in the study. It also discusses the results of the study.

The article examines whether a nicotine-associated visual stimulus (VS) can reinstate nicotine-seeking after extinction in a response-reinstatement model of relapse in rats. It analyzes whether the behavioral effects of the VS are sensitive to pharmacological blockade of nicotinic neurotransmission. It also determines whether active lever reassignment after food training influences nicotine self-administration and the VS-induced reinstatement.

To test whether the anorectic effect of nicotine may be amplified by caffeine. Chewing gums with nicotine and caffeine were administered to 12 healthy young men of normal weight. Different combinations of 0, 1 or 2 mg of nicotine and 0, 50 or 100 mg of caffeine were applied during a 2-h period in a randomized, double blind, cross over design. Appetite sensations were measured using visual analogue scales. Hunger and prospective food consumption were negatively associated with the increasing doses of nicotine, whereas satiety and fullness were positively associated with the increasing doses of nicotine (p < 0.05). Caffeine appeared to amplify the effects of nicotine on hunger and fullness as a caffeine × nicotine × time interaction was observed in these scores (p < 0.05). The 2-mg dose of nicotine in combination with the 100-mg dose of caffeine caused nausea in four of the non-smokers. However, the effects of nicotine and the caffeine × nicotine × time interaction persisted after the exclusion of these subjects. Caffeine added to nicotine chewing gum appears to amplify its attenuating effects on appetite and the combinations of 1-mg of nicotine with caffeine seem to be well tolerated. [ABSTRACT FROM AUTHOR]

The effects of transdermal nicotine maintenance on the subjective, reinforcing, and cardiovascular effects of intravenously administered cocaine, caffeine, and nicotine were examined using double-blind procedures in nine volunteers with histories of using tobacco, caffeine, and cocaine. Each participant was exposed to two chronic drug maintenance phases (21 mg/day nicotine transdermal patch and placebo transdermal patch). Within each drug phase, the participant received intravenous injections of placebo, cocaine (15 and 30 mg/70 kg), caffeine (200 and 400 mg/70 kg), and nicotine (1.0 and 2.0 mg/70 kg) in mixed order across days. Subjective and cardiovascular data were collected before and repeatedly after drug or placebo injection. Reinforcing effects were also assessed after each injection with a Drug vs Money Multiple-Choice Form. Intravenous cocaine produced robust dose-related increases in subjective and reinforcing effects; these effects were not altered by nicotine maintenance. Intravenous caffeine produced elevations on several subjective ratings; nicotine maintenance did not affect these ratings. Under the placebo maintenance condition, intravenous nicotine produced robust dose-related subjective effects, with maximal increases similar to the high dose of cocaine; nicotine maintenance significantly decreased the subjective and reinforcing effects of intravenous nicotine. The results of the present study demonstrate that chronic nicotine maintenance produces tolerance to the effects of intravenous nicotine, but does not affect the subjective or reinforcing effects of cocaine or caffeine. [ABSTRACT FROM AUTHOR]

Rationale. In laboratory tasks nicotine has consistently been shown to improve psychomotor performance. Objectives. The aim of the present experiment was to assess the effects of nicotine on a skilled task of everyday life in smoking and non-smoking healthy adults. Methods. Assessment of handwriting movements of 38 non-deprived smokers and 38 non-smokers was performed following the chewing of gum containing 0 mg, 2 mg or 4 mg of nicotine. A digitising tablet was used for the assessment of fine motor movements. Subjects were asked to perform a simple writing task. Movement time, velocity and acceleration of the handwriting movements were measured. Furthermore, every writing specimen was independently rated by two examiners regarding the quality of handwriting. Results. Kinematic analysis of writing movements revealed that nicotine could produce absolute improvements in handwriting. Following nicotine administration, reduced movement times, increased velocities and more fluent handwriting movements were observed. These improvements were more striking in smokers than in non-smokers. No effects of nicotine were found with regard to the quality of handwriting. Conclusion. The results suggest that nicotine can enhance psychomotor performance to a significant degree in a real-life motor task. [ABSTRACT FROM AUTHOR]

Anxiety may play a role in the initiation of smoking and there is evidence to suggest that sex and age may predetermine responses to nicotine. At present, the greatest increase in smoking is in women and it is often accompanied by dieting. The purpose of the present study was to investigate how the impact of dietary restriction might modify the effects of nicotine in female adult and adolescent rats. The effects of nicotine in the elevated plus-maze test of anxiety were compared in free-feeding animals and those subjected to dietary restriction that reduced body weight to 85% of free-feeding weight. In nondeprived adult females, nicotine (0.05-0.5 mg/kg, s.c.) reduced the percentage of time spent on the open arms, indicating anxiogenic effects. However, the effects of nicotine were dramatically changed in food-restricted adult females and 0.05 mg/kg had a striking anxiolytic effect. No significant effects of nicotine were found in the adolescent female rats, suggesting a role of circulating sex hormones in modulating nicotine's effects on anxiety. However, in the adolescent females, dietary restriction significantly increased the percentages of time spent and entries onto the open arms, without changing closed arm entries, indicating an anxiolytic effect. These results raise the important possibility that, in prepubertal girls, dietary restriction may have anxiolytic effects and this might contribute to the onset of anorexia. Circulating female hormones reduce this effect, but in adult females the combination of dietary restriction and nicotine may have important anxiolytic effects that impact on the initiation of regular smoking. [ABSTRACT FROM AUTHOR]

Consistent with human literature, previous studies identified attention-enhancing effects of nicotine in rats, using a 5-choice task. The present study addressed the influence of repeated exposure to nicotine on these effects. Over six weeks, the effects of nicotine (0.0, 0.05 and 0.2 mg/kg) given ten min before sessions were tested each week. In addition, rats were injected daily two hours after sessions. In the first week, when these post-session injections were of saline for all rats, pre-session nicotine had profound rate-disruptive effects at the larger dose. In weeks 2–6, when half the rats received post-session injections of saline and the other half of nicotine (0.4 mg/kg), the disruptive effects of pre-session nicotine had disappeared and it enhanced attentional performance on all response indices. These effects did not differ significantly between post-session treatment groups or weeks, although they appeared less pronounced in the last two weeks. When tested under modified task parameters in weeks 9 and 10, nicotine (0.1 mg/kg) robustly enhanced performance in both groups despite continuing daily post-session administration of nicotine or saline. These studies provide evidence that, following tolerance to initial disruptive effects, the nicotine-induced attentional enhancement is stable across lengthy periods of chronic exposure. This is important for potential therapeutic applications of the drug and indicates that these effects can be a continuous motive for smoking behavior. [Copyright &y& Elsevier]

This paper reviews findings from placebo-controlled human experimental studies of the effects of nicotine on subjective experience. Studies are grouped according to whether participants were smokers (significantly nicotine deprived, minimally nicotine deprived) or non-smokers. Within each category, studies are also grouped according to method of nicotine administration (e.g., smoked tobacco, nasal spray) and nicotine dose. This review of studies is preceded by a discussion of several methodological issues in studies of nicotine and mood. The principal findings of this review are: (1) there is a linear relationship between nicotine dose and measures of drug high (e.g., head rush, euphoria) in significantly nicotine-deprived smokers; (2) there appear to be few positive or negative main effects of nicotine on mood in minimally nicotine-deprived smokers; (3) nicotine has positive effects (e.g., increases head rush) and negative effects (e.g., increases tension) in non-smokers; (4) stronger effects of nicotine on mood emerge when individual difference variables (e.g., neuroticism) and situational contingencies (e.g., exposure to stressful stimuli) are examined. Additional studies with minimally nicotine-deprived smokers and non-smokers are needed to further specify the conditions under which nicotine affects mood and other subjective experience. The review concludes with a discussion of putative mechanisms that may mediate the interaction between nicotine and moderating variables on affect and with suggestions for future research. [ABSTRACT FROM AUTHOR]

Rationale: Long-term exposure to nicotine is associated with chronic tolerance to its acute effects, adaptation that may lead to tobacco dependence. The time course for loss of this tolerance after cessation of exposure is not known in humans but could relate to risk of smoking relapse. Objectives: We examined changes in responses to nicotine as a function of days, weeks, or years of smoking cessation in formerly dependent smokers to determine at what point sensitivity to nicotine is reinstated (i.e., loss of tolerance). Methods: Acute subjective, cardiovascular, performance, and reinforcing (self-administration) effects of nicotine nasal spray (0–20 µg/kg) were assessed prospectively in men and women smokers before and then day-by-day (study 1) or 3 weeks (study 2) after stopping smoking. A smoking resumption period (study 1) and a group of non-quitting smokers (study 2) were included to control for the passage of time. These effects were also compared cross-sectionally between those who had quit for 1–4 years and those who had for 6–19 years in a separate sample of long-time ex-smokers to determine whether lengthier abstinence causes greater loss of tolerance (study 3). Results: No clear loss of tolerance was observed on any measure in studies 1 or 2, suggesting that chronic tolerance is fully maintained for at least weeks after quitting smoking. Sensitivity to nicotine's effects was also not different as a function of years quit in study 3. Conclusions: Chronic tolerance to nicotine is not lost within several weeks of quitting smoking and may not change even after years of abstinence from tobacco use. [ABSTRACT FROM AUTHOR]