Pharmacological Effects Of Nicotine Research Articles

Microstructural meal pattern analysis reveals a paradoxical acute increase in food intake after nicotine despite its long-term anorexigenic effects

RationaleNicotine 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.ObjectivesThe aim of this study was to elucidate effects of acute nicotine intake on feeding and drinking behavior.MethodsAdult 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.ResultsAt 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.ConclusionsThese 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.

Some aspects of tobacco smoking in the context of alcohol drinking, hangover and mental health problems

The public health relevance of hangover is in its potential effects on occupational safety and performance. Apart from pharmacological effects of ethanol and congeners, psychosocial factors also contribute to morning-after feelings, particularly the emotions of shame and guilt. Tobacco smoking increases the hangover’s incidence and severity, explained by pharmacological effects of nicotine and other smoke constituents. During a drinking binge, many people would smoke more than usual; some intermittent smokers or those who gave up would restart. The hangover “curing” with beer or vodka the next morning (hair of the dog) may contribute to negative affectivity in the long run, as it implies a cycle of alcohol consumption and shame. Some individuals experience a temporary symptomatic relief after a hair of the dog drink. According to our observations, if the “curing” is accompanied by smoking, the elevated mood in some people would more easily shift to dysphoria, irritation or depression. Psychological mechanisms thereof are discussed here. Besides, the problem of smoking in psychiatric hospitals is briefly discussed. In conclusion, smoking can exacerbate hangover symptoms through both toxicological and psychosocial mechanisms. The problem of smoking in the settings of alcoholism and mental health problems should be further investigated.

Evaluation of a Botanical Extract that Mimics the Respiratory Cues of Cigarette Smoke

Introduction: Cigarette addiction results from both pharmacological effects of nicotine and the rewarding effects of associated cues, including respiratory tract sensations.Aims: This study sought to evaluate the initial acceptability of a non-nicotine botanical formulation that provided similar respiratory tract cues.Methods: Two active test products and matching placebos were evaluated. One test product, an e-cigarette-like device, delivered a visible aerosol upon puffing; the other test product delivered an invisible vapour at ambient temperature. Test products delivered a botanical extract with flavourings and vehicle; the placebos delivered flavourings and vehicle only. Sixteen participants had 3-h ad libitum access to each test product and associated placebos, and were deprived of combustible cigarettes for 1 h before and throughout the 3-h evaluation period. Subjects rated the satisfaction (primary outcome) and other sensory qualities of the products. Safety evaluations included pulmonary function testing and monitoring vital signs.Results: Satisfaction ratings (seven-point scale) were significantly greater for the active e-cigarette-like condition; M = 3.18, SD = 1.04 versus M = 2.69, SD = 1.22. Safety evaluations showed no clinically significant changes.Conclusions: The results support the potential acceptability of a non-nicotine cigarette substitute in providing satisfaction to smokers. This approach merits further evaluation for safety and acceptability in tobacco harm reduction and cessation.

Insight into nicotine addiction

The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.

Smoking and Lower Urinary Tract Symptoms.

Pharmacologic effects of nicotine are multifaceted and complicated. Despite numerous studies, the effect of smoking on lower urinary tract functions, have not been yet studied in detail. In this study, we aimed to investigate the effects of smoking addiction on lower urinary tract and sexual functions on the basis of respiratory functions. A total of 186 male patients who have been evaluated between May 2014 and January 2015 were recruited in this study. Smoking history, respiratory symptoms, respiratory function tests, uroflowmetry parameters relating to lower urinary tract symptoms (LUTS), prostate volume, post-voiding residual urine volume and sexual functions of patients have been retrospectively investigated. We determined that as the mean number of cigarettes smoked daily increases, post-void residual urine volume and International Prostate Symptom Score (IPSS) also increase. Moreover in accordance with this finding, mean urinary flow rates and quality of life scores were statistically significantly decreased. In smoking addicts who have high mean package/year, post-void residual urine volume and IPSS levels were increased but proportionately maximum urinary flow rate and average urinary flow rate plus quality of life scores were found to be statistically significantly decreased. In patients with forced expiratory volume in first second:forced vital capacity (FEV1/ FVC) ratio less than 80%, mean urinary flow rates were found to be statistically significantly low. Also, we determined that in smoking addicts who have high mean package/year, erectile functions were statistically significantly impaired. We showed negative impacts of smoking addiction on LUTS, patient's quality of life, and sexual functions.

The effect of nicotine on sign-tracking and goal-tracking in a Pavlovian conditioned approach paradigm in rats

Nicotine (NIC) potently increases operant responding for non-NIC reinforcers, and this effect may depend on drug-mediated increases in incentive motivation. According to this hypothesis, NIC should also potently increase approach to Pavlovian-conditioned stimuli associated with rewards. The present studies explored the effects of NIC on Pavlovian-conditioned approach responses. To do so, liquid dippers were used to deliver an unconditioned stimulus (US; 0.1ml sucrose) after presentation of a conditioned stimulus (CS; 30s illumination of a stimulus light)-both the CS and US were presented in receptacles equipped to monitor head entries. In experiment 1, the CS and US were presented in the same receptacle, but NIC pretreatment (0.4mg/kg base) did not increase conditioned approach responses. Delivery of the sucrose US was then shifted to receptacle in a different location. All rats learned to approach the new US location (goal-tracking) at similar rates. Approach to the CS receptacle (sign-tracking) declined for saline-pretreated rats, but NIC pretreatment increased sign-tracking. In experiment 2, NIC pretreatment increased sign-tracking when the CS and US were spatially separated during acquisition. In experiment 3, NIC pretreatments were replaced with saline, but the effect of NIC persisted for an additional 24 test sessions. The findings suggest that NIC increases incentive motivation and that this effect is long-lasting, persisting beyond the pharmacological effects of NIC.

Nicotine behavioral pharmacology: Clues from planarians

BackgroundNicotine is one of the world's most addictive substances and the primary reason that humans inhale tobacco smoke. The pharmacological effects of nicotine can be investigated in planarians, aquatic flatworms that possess an integrated neural network including cephalic ganglia that some consider the earliest ‘brain’ and spinal cord. Here, we tested the hypothesis that nicotine exposure elicits mammalian-like behaviors in planarians. MethodsPlanarian motility and stereotypy (C-shape hyperkinesias) were quantified following acute nicotine exposure. During repeated nicotine exposure, we investigated the presence of withdrawal, tolerance, behavioral sensitization, and environmental place conditioning. ResultsAcute nicotine exposure increased stereotypical activity and elicited biphasic effects on motility. A low concentration (0.01mM) increased motility whereas higher concentrations (0.3–10mM) elicited the opposite effect. Planarians exposed to nicotine (0.03mM) for 60min and then tested in water displayed reduced motility that was not observed during exposure to water, acute nicotine, or continuous nicotine. Nicotine-treated planarians withdrawn from the drug for 3 days before being challenged with nicotine displayed behavioral sensitization at low concentrations (0.1, 0.3mM) but tolerance at higher concentrations (1, 3mM). Planarians conditioned with nicotine in the ambient light (non-preferred environment) displayed a reduction in their natural preference for a dark environment. ConclusionsThe present results suggest nicotine elicits mammalian-like effects in planarians, including decreased motility and increased stereotypy following acute administration and abstinence-induced withdrawal, behavioral sensitization, tolerance, and place conditioning during repeated exposure.

Influence of nicotine on the coronary circulation of the isolated heart of the cat

Abstract Nicotine administered to the isolated perfused heart of the cat produces initial bradycardia followed by long-lasting tachycardia and enhancement of the strength of contractions. The coronary flow after a reduction shows a prolonged increase that continues after the heart hyperactivity has ceased. When nicotine was given after hexamethonium or after reserpine pretreatment, the cardio-stimulation disappeared and only reduction of the coronary flow was obtained. It is concluded that the complexity of the pharmacological effect of nicotine on the coronary flow of the isolated heart preparation depends on an indirect vasodilator action mediated by the heart stimulation due to liberation of intracardiac catecholamines and also on vasoconstriction due to a direct effect of the drug on the coronary vasculature.

Histamine H 1 antagonist treatment with pyrilamine reduces nicotine self-administration in rats

Nicotine has been definitively shown to be critically involved in the neural bases of tobacco addiction. However, nicotine releases a wide variety of neurotransmitters. Nicotine-induced dopamine release has been shown to play a key role in facilitating nicotine self-administration. Other transmitter systems may also play important roles in the pharmacological effects of nicotine and may provide important leads for combating nicotine self-administration. Clozapine, an antipsychotic drug, which blocks a variety of different transmitter receptors including serotonin 5HT 2 and histamine H 1 receptors, has been found to decrease smoking. Previously we found that the serotonin 5HT 2 antagonist, ketanserin, significantly reduced nicotine self-administration. In the current study, we assessed histamine H 1 receptor interaction with nicotine self-administration. Young adult female Sprague–Dawley rats were fitted with IV catheters and trained to self-administer nicotine (0.03 mg/kg/infusion). Acute doses of 40 mg/kg of pyrilamine, a histamine H 1 antagonist, significantly reduced nicotine self-administration. We also found that repeated injections (20 mg/kg) or chronic infusion via osmotic minipumps (50 mg/kg/day) of pyrilamine also significantly decreased nicotine self-administration. The peripherally restricted H 1 antagonist ebastine was ineffective in reducing nicotine self-administration, pointing to central H 1 receptor blockade as key for the effectiveness of pyrilamine. H 1 antagonists may be a promising avenue to explore for new treatments to aid smoking cessation.

Sex differences in response to nicotine in C57Bl/6:129SvEv mice

Human studies suggest that smoking behavior in men may depend more on the pharmacological effects of nicotine, whereas in women, this behavior may rely more on nonpharmacological factors associated with smoking. Investigation of these parameters in mice may also reveal sex differences. Male and female C57Bl/6:129SvEv hybrid mice were exposed to increasing concentrations of nicotine in a voluntary oral nicotine consumption paradigm in which we measured fluid consumption over time and dose. Separate cohorts of mice were exposed to nicotine in a place-conditioning paradigm, and preference was determined. These behavioral models were used to examine sex differences in mice as they rely on pharmacological as well as nonpharmacological factors. Mice exposed to nicotine or saline also were tested for sex differences in locomotor-activating effects of nicotine and in analgesia using standard activity monitoring and hot-plate tests. Females responded more to the conditioned rewarding effects of nicotine compared with males. Males, however, seemed more responsive to the pharmacological aspects of nicotine by reducing nicotine drinking at higher concentrations; females maintained consistent levels of intake over several doses of nicotine. Male and female mice demonstrated similar locomotor and antinociceptive responses to nicotine. These data suggest that place-conditioning and two-bottle choice paradigms may be more sensitive measures of sexual dimorphism in the C57BL/6:129SvEv hybrid mouse than are locomotor or nociception assays.

Empirical, Logical and Philosophical Arguments Against Cigarette Smoking as a Pharmacologically Compelled Act

The fundamental hypothesis of the disease model of nicotine addiction states that, following a regime of chronic smoking, further smoking becomes a pharmacologically compelled rather than a chosen act. Despite it’s public and professional popularity as an explanation for why people continue to smoke in spite of a deteriorating quality of life, the validity of this hypothesis has been critically undermined by the state of evidence in four domains: inconclusive empirical evidence of withdrawal severity as a potent predictor of quit outcome; methodological problems concerning the measurement of factors which maintain smoking; logical problems with the interpretation of factors which maintain smoking, in particular, failures to discriminate reflexive and mediated actions in explanations of why people smoke; and philosophical problems with conceptualisations of human action as determined rather than willed. In light of these problems, it is argued that evidence on the nature of nicotine addiction is not well explained by the disease model, but rather, posits smoking primarily as a decision-making process influenced peripherally by the pharmacologic effects of nicotine on the brain and body.

Establishment and evaluation of a nicotine-treatment and -withdrawal rat model

Objective:To establish a nicotine-treatment and-withdrawal rat model and to evaluate its characteristics and application through analyzing 3 parameters.Methods:Male Sprague-Dawley rats,aged 10-11 weeks old,were randomly divided into normal saline group(subcutaneous injection of saline [0.5 ml/kg] for 6 weeks),nicotine-treated group(injection with nicotine [0.5 ml/kg,3 mg/(kg·d)] for 6 weeks),and nicotine-withdrawn group(injection with nicotine [0.5 ml/kg,3 mg/(kg·d)] for 3 weeks and followed by saline injection for additional 3 weeks).Body weight,food intake,and water intake of animals were recorded during the treatment in 3 groups.The model was evaluated through analyzing body weight,serum parameters and adipose tissue weights.Results:The body weight of rats,as well as the serum levels of triglyceride and insulin,were all decreased after nicotine treatment;the weights of subcutaneous fat,visceral fat and periaortic fat were also decreased.The above indicators increased after withdrawal of nicotine.Conclusion:The established model can be used to study multiple pharmacological effects of nicotine;it can also be used for smoking and smoking cessation related studies.

Expectancy and pharmacology influence the subjective effects of nicotine in a balanced-placebo design.

The expectancy and pharmacological effects of nicotine (0.60 mg) on memory and the subjective effects of cigarettes were examined by using a balanced-placebo design (i.e., expect either nicotine or no nicotine and receive either nicotine or no nicotine). A total of 120 college students who smoke were assigned to 1 of the 4 experimental groups, then rated the cigarettes on a number of dimensions and completed questionnaires on smoking urges, tension, and energy. Participants also completed tests of memory as well as predictions of memory. Pharmacology played a stronger role than expectancy in most ratings of the cigarettes, but significant effects of expectancy did emerge for feelings of increased wakefulness, concentration, calming, cigarette satisfaction, and hunger reduction. The presence of nicotine significantly reduced smoking urges, but expectancy alone reduced tension after smoking. Neither variable produced significant effects on memory or memory predictions. These findings demonstrate that nonpharmacological factors can play an important role in the self-reported effects of nicotine.

Inhibition of Nicotine Metabolism by Methoxysalen: Pharmacokinetic and Pharmacological Studies in Mice

Studies were undertaken to examine whether methoxsalen (9-methoxyfuro[3,2-g][1]benzopyran-7-one), a specific and relatively selective inhibitor of human CYP2A6, inhibited CYP2A5-mediated nicotine metabolism in vitro. Furthermore, studies were performed in vivo to determine whether methoxsalen would modulate acute nicotine pharmacokinetics and pharmacological effects (antinociception and hypothermia) in the ICR mouse. Our results demonstrated that methoxsalen competitively inhibits in vitro nicotine metabolism in mice. The inhibition was potent, as seen in human inhibition studies, with a Ki of 0.32 microM. In addition, we found that administration of methoxsalen significantly increased the plasma half-life of nicotine (approximately doubled) and increased its area under the curve compared with saline treatment. There was a dose-dependent enhancement in the pharmacological effects of nicotine (body temperature and analgesia) after methoxsalen treatment. Methoxsalen prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg) for periods up to 180 min postnicotine administration. Furthermore, this prolongation in nicotine's effects after methoxsalen was associated with a parallel prolongation of nicotine plasma levels in mice. These data strongly suggest that variation in the rates of nicotine metabolic inactivation substantially alter nicotine's pharmacological effects. In conclusion, these results confirmed that methoxsalen did indeed inhibit the conversion of nicotine to cotinine both in vitro and in vivo. They also suggest that mice may represent a suitable model for studying variation in nicotine metabolism and its impact on mechanisms of nicotine dependence, including the use of inhibitors to reduce nicotine metabolism.

Differential effects of nicotine on alcohol consumption in men and women

Nicotine and alcohol are frequently co-used, suggesting that use of one drug may facilitate use of the other. Furthermore, because men and women differ in their responses to both drugs, it is possible that men and women also differ in their responses to the combination of nicotine and alcohol. This experiment was designed to investigate the effects of nicotine on consumption and subjective and physiological effects of alcohol in healthy male and female social drinkers. Healthy light smoking, social drinkers (22 men and 12 women) participated in a three-session, double-blind within-subject study. They were pretreated with transdermal nicotine (7 or 14 mg) or placebo, followed two h later by an alcoholic beverage, and subsequent opportunities to "purchase" and consume more of the same drink. Outcome measures included the number of alcoholic beverages consumed and subjective and physiological effects. Nicotine increased alcohol consumption in men, whereas it decreased alcohol consumption in women. These effects were even more pronounced after excluding participants reporting nausea after nicotine administration. Nicotine alone increased subjective arousal in men but decreased positive mood in women. Nicotine increased the sedative-like effects of alcohol in both sexes. These findings indicate that both the subjective effects of nicotine and the effects of nicotine on alcohol consumption differ markedly in men and women. The findings extend existing data on sex differences in the effects of either nicotine or cigarette smoking on alcohol consumption, and support the idea that the pharmacological effects of nicotine may differ in men and women.

Time-dependent changes in transcriptional profiles within five rat brain regions in response to nicotine treatment

Many years of behavioral and neurobiology studies have demonstrated broad physiological and pharmacological effects of nicotine on the central nervous system (CNS). However, the gene expression profiles associated with these effects are largely unknown. In this study, we characterized gene expression profiles in the prefrontal cortex, striatum, hypothalamus, amygdala and ventral tegmental area of the rat brain in response to subacute and chronic systemic nicotine administration using a pathway-focused microarray developed in this laboratory that contains 638 sequence-verified genes representing broad, yet targeted, biological functions. By comparing the regional effects of nicotine treatment on gene expression levels, we derived the expression profiles of targeted genes and gene families responding to the new environment created by nicotine throughout the complex connections of the CNS. While the expression of many genes was modulated by nicotine in several regions, only a few were co-modulated in multiple brain regions, suggesting region-specific transcriptional responses. Cluster analysis of significantly altered genes within each brain region over the course of nicotine treatment indicated the genes could be grouped into clusters. Subsequent ANOVA analysis demonstrated these clusters within each brain region to be significantly different at most time points. The clusters were comprised of broad functional groups, such as signaling, neurotransmission and protein modifications, demonstrating unique expression patterns within each region. Using a systematic approach to compare the different regional responses to nicotine administration will eventually provide a better understanding of how the different brain regions responding to this drug.

EFFECTS OF CIGARETTE SMOKING ON COGNITIVE PROCESSING

Several previous studies have reported that cigarette smoking enhances performance of cognitive processing. These enhancements are generally attributed to the pharmacological effects of nicotine, while there is some debate whether the effects of smoking/nicotine are a result of recovery from abstinence. Evoked potentials (EPs) and event related potentials (ERPs) of the brain have been applied as an index of information processing in a wide variety of normal and cognitive impaired subjects. This study was carried out on 20 healthy students (23 ± 2.3 years old) from the medical faculty of City University. Study population comprised ten chronic cigarette smokers consuming an average of 14 ± 4.2 cigarettes per day, with a history of smoking for more than one year. Ten non--smokers served as control. Standard oddball paradigm was presented, and EEG activity was recorded at the Fz, Cz, Pz electrode sites. Twenty responses to target stimuli were averaged at each location. N1, P2, N2, and P300 components were evaluated in these recordings. Amplitudes were measured relative to prestimulus baseline, and peak latencies were defined as the time point of maximum amplitude. It was found that there were no significant differences between either N1, P2, N2, P300 amplitudes or peak latency values of cigarette smokers and non smokers. As a result, chronic cigarette smoking generally does not improve cognitive processing

Pharmacologic and sensorimotor components of satiation in cigarette smoking

To examine mechanisms underlying satiation in cigarette smoking, 18 smokers received intravenous (iv) nicotine, alone or in combination with denicotinized cigarette smoke. Nicotine was administered using programmed presentations of either pulsed injections or continuous infusions, with iv saline serving as a control. A high-nicotine cigarette smoke condition (usual brand) was also presented. During each of the six test sessions, subjects were allowed to puff on their usual brands of cigarette ad libitum while the programmed satiation conditions were in force. Administration of iv nicotine caused a small suppression of ad libitum smoking behavior; denicotinized smoke produced a significantly larger reduction, showing that short-term satiation is more dependent on the presentation of smoke than delivery of nicotine per se. However, denicotinized smoke alone did not have as much effect as puffs from the usual brands of cigarettes. The combination of iv nicotine and denicotinized smoke puffs produced equivalent satiation to that of the usual brand. Cigarette craving and negative affect were partially relieved by iv nicotine presentations as well as by denicotinized smoke, and again the combination of iv nicotine and denicotinized smoke approximated the effects of the usual brand. The results of this study underscore the importance of both sensorimotor aspects of smoking and the pharmacologic effects of nicotine in tobacco dependence.

Dissociating nicotine and nonnicotine components of cigarette smoking

To dissociate the sensorimotor aspects of cigarette smoking from the pharmacologic effects of nicotine, smokers rated the subjective effects of nicotine-containing or denicotinized cigarettes, and intravenous (IV) nicotine or saline infusions. Three groups of participants ( n=20 per group) received either: (1) continuous nicotine, (2) pulsed nicotine, or (3) saline. Each group was exposed to an IV condition once while smoking a denicotinized cigarette and once while not smoking, in a 3×2 mixed design. A fourth group ( n=20) received saline while smoking their usual brand of cigarette. The dose and rate of nicotine administration were individualized based on previous measures of ad lib smoke intake. Denicotinized cigarette smoke significantly reduced craving and was rated significantly more satisfying and rewarding than the no-smoking conditions. IV nicotine reduced craving for cigarettes, and increased ratings of lightheadedness and dizziness. However, no significant satisfaction or reward was reported after IV nicotine. The combination of IV nicotine and denicotinized cigarette smoke produced effects similar to those of smoking the usual brand of cigarette. The results suggest that sensorimotor factors are critical in mediating the immediate subjective response to smoking, and that the immediate subjective effects of nicotine administered in doses obtained from cigarette smoking are subtle. Thus, addressing smokers' needs for both for the sensorimotor aspects of smoking as well as for the direct CNS effects of nicotine may be critical in enhancing smoking cessation treatment outcome.

Nicotine administration enhances NPY expression in the rat hypothalamus

Epidemiological studies have shown an inverse relationship between cigarette smoking and body weight. In rodents, a negative correlation between nicotine and body weight has been reported, but this observation was largely derived from studies where relatively high doses of nicotine (∼12 mg/kg/day) were used. In the current study, we showed that a negative relationship also holds for low doses of nicotine that are comparable to that consumed by average human smokers (<6 mg/kg/day). We also demonstrated that 14 days of nicotine administration (4 mg/kg/day) reduced average daily food intake by 19.5% ( P<0.01) in the free-feeding nicotine-treated group compared to saline controls. No significant differences in body weight were detected between the nicotine-treated and pair-fed groups. To determine whether the effects of nicotine on food intake and body weight were related to neuropeptide Y (NPY) expression, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and radioimmunoassay were utilized to measure NPY mRNA and peptide levels in various regions of the hypothalamus. Significantly higher levels of NPY mRNA (ca. 20–50%) and peptide (ca. 24–69%) were only detected in the nicotine-treated groups. In addition, significantly higher NPY contents were also obtained in two hypothalamic areas of pair-fed control animals. In summary, our data suggest that the pharmacological effects of nicotine on food intake and body weight may be mediated by changes in hypothalamic NPY levels, a neuropeptide that is pivotal to the hypothalamic regulation of food intake.