Acute Effects Of Nicotine Research Articles

Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala

Nicotine intake is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in rodents and humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n = 88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to enhanced physiological arousal to learned threats and overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety.

Initial evidence of the acute effect of electronic nicotine delivery system use on energy intake.

Previous work has aimed to disentangle the acute effects of nicotine and smoking on appetite with mixed findings. Electronic nicotine delivery systems (ENDS) have yet to be examined in this regard despite evidence of use for weight control. The present study tested the influence of an ENDS on acute energy intake and associated subjective effects. Participants (n = 34; 18-65 years) with current ENDS use completed two randomly ordered clinical lab sessions after overnight abstinence from tobacco/nicotine/food/drinks (other than water). Sessions differed by the product administered over 20 min: active (20 puffs of a JUUL ENDS device; 5% nicotine tobacco-flavored pod) or control (access to an uncharged JUUL with an empty pod). About 40 min after product administration, participants were provided an ad lib buffet-style meal with 21 food/drink items. Subjective ratings were assessed at baseline, after product use, and before/after the meal. Energy intake (kcal) was calculated using pre-post buffet item weights. Repeated measures analyses of variance and pairwise comparisons were used to detect differences by condition and time (α < .05). Mean ± standard error of the mean energy intake did not differ significantly between active (1011.9 ± 98.8 kcal) and control (939.8 ± 88.4 kcal; p = .108) conditions. Nicotine abstinence symptoms significantly decreased after the active condition, while satiety significantly increased. Following the control condition, satiety remained constant while hunger significantly increased relative to baseline. Findings indicate that acute ENDS use did not significantly impact energy intake, but there was an ENDS-associated subjective increase in satiety and relative decrease in hunger. Results support further investigation of ENDS on appetite. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Acute nicotine intake increases feeding behavior through decreasing glucagon signaling in dependent male and female rats

Chronic use of nicotine is known to dysregulate metabolic signaling through altering circulating levels of feeding-related hormones, contributing to the onset of disorders like type 2 diabetes. However, little is known about the acute effects of nicotine on hormonal signaling. We previously identified an acute increase in food intake following acute nicotine, and we sought to determine whether this behavior was due to a change in hormone levels. We first identified that acute nicotine injection produces an increase in feeding behavior in dependent rats, but not nondependent rats. We confirmed that chronic nicotine use increases circulating levels of insulin, leptin, and ghrelin, and these correlate with rats' body weight and food intake. Acute nicotine injection in dependent animals decreased circulating GLP-1 and glucagon levels, and administration of glucagon prior to acute nicotine injection prevented the acute increase in feeding behavior. Thus, acute nicotine injection increases feeding behavior in dependent rats by decreasing glucagon signaling.

Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats

Nicotine is a significant public health concern because it is the primary pharmacological agent in tobacco use disorder. One neural system that has been implicated in the symptoms of several substance use disorders is the melanin-concentrating hormone (MCH) system. MCH regulates various motivated behaviors depending on sex, yet little is known of how this interaction affects experience with drugs of abuse, particularly nicotine. The goal of this study was to determine the effect of MCH receptor antagonism on experience-dependent nicotine-induced locomotion after chronic exposure, particularly on the expression of locomotor sensitization. Adult female and male Wistar rats were given saline then cumulative doses of nicotine (0.1, 0.32, 0.56, and 1.0 mg/kg) intraperitoneally to determine the acute effects of nicotine (day 1). Next, rats were treated with 1.0 mg/kg nicotine for 6 days, given an identical series of cumulative doses (day 8), and then kept in a drug-free state for 6 days. On day 15, rats were pretreated with vehicle or the MCH receptor antagonist GW803430 (10 or 30 mg/kg) before another series of cumulative doses to assess response to chronic nicotine. After vehicle, male rats increased nicotine locomotor activation from day 1 to day 15, and both sexes showed a sensitized response when normalized to saline. The lower dose of GW803430 decreased locomotion compared to vehicle in females, while the higher dose decreased locomotion in males. Both sexes showed nicotine dose-dependent effects of GW803430, strongest at lower doses of nicotine. Controlling for sex-based locomotor differences revealed that females are more sensitive to GW803430. The high dose of GW803430 also decreased saline locomotion in males. Together, the results of our study suggest that MCH is involved in the expression of nicotine locomotor sensitization, and that MCH regulates these nicotine behavioral symptoms differently across sex.

Lifetime caffeine and adolescent nicotine exposure in mice: effects on anxiety-like behavior and reward.

Caffeine consumption occurs throughout life, while nicotine use typically begins during adolescence, the period when caffeine-nicotine epidemiological association begins in earnest. Despite that, few studies in animal models parallel the pattern of coexposure that occurs in humans. Therefore, the neurobehavioral consequences of the association between these drugs remain unclear. Here, we exposed Swiss mice to lifetime caffeine. Caffeine solutions of 0.1 g/L (CAF0.1), 0.3 g/L (CAF0.3), or water (CTRL) were used as the sole liquid source, being offered to progenitors until weaning and, after that, directly to the offspring until the last day of adolescent behavioral evaluation. The open field test was used to evaluate acute effects of nicotine, of lifetime caffeine and of their interaction on locomotion and anxiety-like behavior, while the conditioned place preference test was used to assess the impact of caffeine on nicotine (0.5 mg/Kg, i.p.) reward. Frontal cerebral cortex dopamine content, dopamine turnover, and norepinephrine levels, as well as hippocampal serotonin 1A receptor expression were assessed. CAF0.3 mice exhibited an increase in anxiety-like behavior when compared to CAF0.1 and CTRL ones, but nicotine coexposure mitigated the anxiogenic-like caffeine-induced effect. Distinctively, caffeine had no effect on locomotion and failed to interfere with both nicotine-induced hyperactivity and place preference. There were no significant effects on dopaminergic and serotonergic markers. In conclusion, although caffeine did not affect nicotine reward, considering the strong association between anxiety disorders and tobacco consumption, caffeine-induced anxiety-like behavior advises limiting its consumption during development, including adolescence, as caffeine could be a risk factor to nicotine use.

Overdose symptoms and positive affect in never-established smokers are moderated by nicotine patch type: A between-subjects experimental investigation

Background: A growing number of studies have assessed the effects of acute nicotine on affect, cognition, and brain activity in never-established smokers in attempts to identify mechanisms by which nicotine promotes progression to dependence. However, these acute administration studies have not adequately addressed the problem of potential adverse side effects due to lack of tolerance, such as nausea, feelings of sickness, lightheadedness, and general negative affect and malaise – a term referred to as nicotine overdose events (NODEs). Thus, we report the first study to carefully characterize the prevalence, intensity, and effects of NODEs in never-established-smokers after acute nicotine administration. Methods: We compared the subjective effects of two different 7 mg nicotine patches that have different pharmacokinetics on never-established smokers (n = 67). One patch produces gradual increases in blood nicotine and the other produces more rapid increases in blood nicotine. Results: The findings suggest that in never-smokers, the lowest dose (7 mg) of rapid blood nicotine-rise patches are associated with a high prevalence of NODEs (45.83%) and decreased positive affect (PA) (54.17%) compared to a placebo patch (8.34% for NODEs and 33.34% for PA). The slow-rise patch did not significantly affect nicotine overdose symptoms or PA. Conclusions: Fast blood-rise nicotine patches may not be an ecologically valid method of nicotine delivery to never-smokers, while slow-rise nicotine patches, lower dose, and self-paced dosing may be more appropriate in this population. Findings also highlight the importance of the careful assessment of NODES in this population.

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

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

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.

Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players.

There is interest in whether nicotine could enhance attention in sporting performance, but evidence on the acute effect of nicotine on physical response and sports performance in baseball players remains scant. This was an observational study to examine whether nicotine gum chewed before exercise could provide acute effects on physiological responses and sport performance. Accordingly, heart rate variability (HRV), saliva cotinine concentration and α-amylase activity, cognitive function, muscle strength, and baseball-hitting performance were measured. Thirteen healthy male non-smoker baseball players were recruited. Conducting two sequences with 7-day intervals, they chewed nicotine gum (nicotine group) or flavor-matched placebo gum (placebo group) for 30 min. HRV and saliva analyses were conducted before gum consumption (S1), after gum consumption (S2), and after test completion (S3). Cognitive, muscle strength, and baseball-hitting performance tests were performed after nicotine or placebo gum chewing. The outcomes of all assessed variables were compared within and between the groups. Significant changes in HRV, α-amylase, testosterone, and cortisol were observed in the nicotine group at S2 and S3 (p < 0.05). Compared with the placebo group, the nicotine group exhibited enhanced motor reaction times, grooved pegboard test (GPT) results on cognitive function, and baseball-hitting performance, and small effect sizes were noted (d = 0.47, 0.46 and 0.41, respectively). Nicotine could induce changes in endocrine and sympathetic nerve activity and enhance cognitive function and baseball-hitting performance. However, no increase in muscle strength was observed after nicotine intake.

Anhedonia in Nicotine Dependence.

Prior findings indicate that trait anhedonia enhances the likelihood of becoming a tobacco smoker, and preliminary evidence suggests that smoking abstinence leads to anhedonic states in some individuals and situations, and nicotine administration reduces anhedonic states. Nevertheless, many vital questions exist concerning relationships between anhedonia and nicotine dependence, including situational and individual difference factors that may moderate the strength of these associations. This chapter provides a critical review of the literature assessing relationships of anhedonia to nicotine dependence and the effects of acute nicotine through the lenses of the Research Domain Criteria's (RDoC) Positive Valence Systems (NIMH, RDoC changes to the matrix (CMAT) workgroup update: proposed positive valence domain revisions. A report by the national advisory mental health council workgroup on changes to the research domain criteria matrix, 2018) and the Situation x Trait Affective Response (STAR) model of nicotine's effects and nicotine dependence (Gilbert, Smoking individual differences, psychopathology, and emotion. Taylor and Francis, Washington, DC, 1995; Gilbert, Hum Psychopharmacol Clin Exp 12:S89-S102, 1997). The effects of nicotine and nicotine withdrawal on subjective, behavioral, and brain indices vary across the three RDoC Positive Valences Systems (Reward Responsiveness, Reward Learning, and Reward Valuation) in a manner that supports the research and potential clinical utility of using RDoC criteria and the STAR model to guide research and clinical innovation. We provide a revision of the STAR model that incorporates the three RDoC Positive Valence Systems with evidence that nicotine's effects on hedonic and affective processes vary as a function of the dominance/salience of (1) situational hedonic and affective cues and task/active coping cues, and (2) state executive functioning level/capacity and state reward sensitivity such that these effects of nicotine are maximal during states of suboptimal cognitive functioning and reward sensitivity, combined with low situational stimulus salience and low task-related cues/demands.

The effects of inhaled flavors on intravenous nicotine.

Menthol is the only available flavor in combusted tobacco cigarettes; however, e-cigarettes are available in thousands of flavors. Research on flavors and rewarding properties of nicotine is limited. The present study sought to examine the acute rewarding effects of flavors inhaled from an e-cigarette, in combination with intravenous (IV) nicotine among cigarette smokers. In the present study, 24 menthol-preferring young adult (aged 18 to 30) cigarette smokers were tested under 3 different e-cigarette flavor conditions (menthol, green apple, or menthol + green apple) in a within-subject cross-over design. During each test session, each participant received 3 IV infusions (saline, 0.25 mg/70 kg nicotine, 0.5 mg/70 kg nicotine) administered 1 hr apart. The main outcome measures assessed cardiovascular, subjective, and cognitive domains. Compared with green apple or green apple + menthol, menthol produced higher ratings of "cooling" (ps < 0.01). Craving was rated higher following administration of green apple and the combined menthol + apple flavor compared to menthol alone (ps < 0.05). As expected, IV-nicotine dose-dependently increased the ratings of subjective liking/disliking and peak heart rate, improved cognitive performance, and reduced smoking urges (all ps < 0.05). These subjective, cognitive, and physiological effects of nicotine were not affected by any flavor condition. The present findings did not support an interaction between IV-nicotine dose and inhaled flavor for acute effects of nicotine. Green apple flavor, alone or in combination with menthol, could result in higher craving or insufficiently alleviate craving, relative to menthol flavor alone. Additional research is warranted to examine extended exposure to inhaled flavors on the rewarding and addictive effects of nicotine. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers.

Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine. Light smokers (n = 116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence 'risk' allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured. Across the sample, reward responsiveness was greater following nicotine compared to placebo (p = 0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received placebo first (p = 0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p < 0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p = 0.010) and were associated with blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine. These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine's effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population. Individuals carrying genetic risk factors associated with nicotine dependence(rs16969968 A-allele carriers) and those with higher levels of depressive personality traits, showmore pronounced increases in reward learning following acute nicotine exposure. These findingssuggest that genetic and personality factors may drive individual differences in smoking trajectoriesin young light smokers by altering the degree to which nicotine enhances reward processing. NCT02129387 (pre-registered hypothesis: www.clinicaltrials.gov).

Abstract 13788: Acute Administration of Nicotine Induces Transient Elevation of Blood Pressure and Increases Myocardial Infarct Size in an Acute Myocardial Ischemia/reperfusion Rat Model

Introduction: Nicotine is a major bioactive component in tobacco cigarettes and electronic cigarettes. Despite the fact that smokers are at higher risk of experiencing an acute myocardial infarction (AMI), there are few studies that have examined the acute effects of nicotine on AMI.To address this issue, our present study was to examine the acute effects of nicotine on myocardial infarct size, no reflow, cardiac hemodynamics and cardiac function in a rat myocardial infarct model. Methods: Forty-six female Sprague-Dawley rats were randomly divided into nicotine group and control group (n=23/group) and received an intravenous loading dose of nicotine at 2.0 μg/kg/min or saline for 30 minutes before starting coronary artery occlusion, then followed by a maintenance dose 0.35 μg/kg/min of nicotine to the end of 3.5 hours of occlusion (30 minutes) and reperfusion (3 hours). Results: At baseline, there were no difference between the two study groups, in systolic blood pressure (BP in mmHg) (nicotine, 69.0±2.7; control, 69.3±4.4; p &gt; 0.05), or diastolic BP (nicotine, 45.7±3.2; control, 48.2±4.2; p &gt; 0.05). Nicotine initially increased systolic BP (nicotine, 97.0±8.6; control, 69.2±3.3, p &lt;0.05) and diastolic BP (nicotine, 65.6±6.4; control, 47.4±3.1, p &lt; 0.01) at 10 minutes after starting injection of the loading dose; pressures dropped to control levels in both groups at 30 minutes. During occlusion/reperfusion, the BP and heart rate were not altered by nicotine. Nicotine significantly increased myocardial infarct size as a percentage of the ischemic risk zone compared to the controls (nicotine, 54.9 ± 1.9 %; control, 48.6 ± 2.7 %, p &lt; 0.05), but nicotine did not affect the no-reflow size (nicotine, 34.8 ± 3.10 %; control, 33.7 ± 3.0%, p &gt; 0.05). Nicotine did not alter fractional shortening assessed by echocardiography. Conclusions: Nicotine infusion can transiently increase blood pressure in anesthetized rats. During coronary occlusion and reperfusion, nicotine increased myocardial infarct size, but did not affect hemodynamics or fractional shortening, suggesting that the increase in infarct size was not simply due to an increase in oxygen demand due to altered afterload, heart rate or contractility, but may reflect a more direct effect on the myocardium.

The acute and repeated effects of cigarette smoking and smoking-related cues on impulsivity.

Impulsivity may be a risk factor that increases vulnerability to nicotine dependence. However, nicotine exposure itself may directly increase impulsivity. This is a secondary analysis of the first study in a controlled laboratory setting, which assessed the effects of nicotine administration (acute and repeated) and exposure to smoking cues on behavioural impulsivity in humans (ClinicalTrials.gov Identifier: NCT01395797). Twenty-seven smokers completed three tasks to assess behavioural impulsivity (the Immediate Memory Task and the Delayed Memory Task assessing response initiation, and the GoStop Task assessing response inhibition) following: (i) 4 days of cigarette smoking (nicotinised or denicotinised cigarette); (ii) acute cigarette smoking (nicotinised); and (iii) exposure to smoking-related cues. Four days of nicotinised cigarette smoking (vs. denicotinised) did not significantly increase Immediate Memory Task, Delayed Memory Task and GoStop scores. However, acute cigarette smoking increased GoStop impulsivity, but only following 4 days of smoking nicotinised cigarettes (P < 0.05). Exposure to smoking-related cues had no statistically significant effect on impulsivity. Our results suggest that repeated nicotine exposure may sensitise subsequent acute nicotine effects on behavioural impulsivity in heavy smokers.

Acute administration of nicotine induces transient elevation of blood pressure and increases myocardial infarct size in rats

AimsWe investigated the acute effects of nicotine on myocardial infarct size, no reflow, hemodynamics and cardiac function in an acute myocardial ischemia and reperfusion infarction rat model. Main methodsFemale Sprague-Dawley rats (n = 23/group) received an intravenous loading dose of nicotine at 2.0 μg/kg/min or saline control for 30 min before starting coronary artery occlusion, then followed by a maintenance dose 0.35 μg/kg/min of nicotine to the end of 30 min occlusion and 3 h reperfusion. Key findingsAt baseline, there was no difference in systolic blood pressure (BP in mmHg) (nicotine, 69.0 ± 2.7; control, 69.3 ± 4.4; p = NS) or diastolic BP (nicotine, 45.7 ± 3.2; control, 48.2 ± 4.2; p = NS) between groups. Nicotine administration initially increased systolic BP (nicotine, 97.0 ± 8.6; control, 69.2 ± 3.3, p < 0.0001) and diastolic BP (nicotine, 65.6 ± 6.4; control, 47.4 ± 3.1, p = 0.0003) at 10 min after starting injection of the loading dose; BP dropped to control levels in both groups at 30 min. During occlusion and reperfusion, the BP and heart rate were not altered by nicotine. Nicotine significantly increased myocardial infarct size as a percentage of the ischemic risk zone compared to the controls (nicotine, 54.9 ± 1.9; control, 48.6 ± 2.7, p < 0.05), but nicotine did not affect the no-reflow size and heart function. SignificanceWhile acute nicotine only transiently elevated blood pressure, it did not affect hemodynamic parameters during coronary artery occlusion. Nicotine increased myocardial infarct size, suggesting that the increase in infarct size was not simply due to an increase in oxygen demand due to altered afterload, heart rate, or contractility, but may have been due to a more direct effect on the myocardium.

Prenatal nicotine exposure affects cardiovascular function and growth of the developing fetus.

Effects of nicotine on fetal hemodynamics are not well known, especially in the first trimester fetus. We investigated the acute and chronic effects of nicotine on hemodynamics in pregnant mice and their fetuses using ultrasound. Postnatal health status including growth and hemodynamics was also examined. To investigate the acute effects of nicotine on fetal hemodynamics, we injected nicotine 0.2 mg/kg subcutaneously into pregnant mice on gestational days (GD) 9.5, 11.5 and 13.5 and compared with saline-injected group. To determine the chronic effects of nicotine on fetal hemodynamics, we administered nicotine in drinking water (0.1 mg/mL) to pregnant mice from GD 6.5 until they gave birth and compared hemodynamics with water-administered mice. Regarding the acute effects of nicotine, we found no intergroup difference in maternal hemodynamics; however, fetal blood flow through the dorsal aorta, carotid artery and umbilical artery tended to decrease, particularly on GD 11.5. Regarding the chronic effects of nicotine, we observed no intergroup difference in maternal body weight changes and hemodynamics; however, blood flow to all fetal organs tended to be lower in the nicotine water group than in the water group with significant difference on GD 13.5. The offspring of the nicotine water group had significantly low birth weights and continued to have low body weight until 9 weeks of age. In addition, these offspring developed postnatal cardiac hypertrophy. Nicotine adversely affects fetal hemodynamics acutely and chronically in early pregnancy, potentially leading to fetal tissue hypoxia, intrauterine growth restriction and adverse postnatal health effects.

The acute effects of nicotine on corticostriatal responses to distinct phases of reward processing.

Nicotine enhances the reinforcement of non-drug rewards by increasing nucleus accumbens (NAcc) reactivity to anticipatory cues. This anticipatory effect is selective as no clear evidence has emerged showing that nicotine acutely changes reward receipt reactivity. However, repeated rewarding experiences shift peak brain reactivity from hedonic reward outcome to the motivational anticipatory cue yielding more habitual cue-induced behavior. Given nicotine's influence on NAcc reactivity and connectivity, it is plausible that nicotine acutely induces this shift and alters NAcc functional connectivity during reward processing. To evaluate this currently untested hypothesis, a randomized crossover design was used in which healthy non-smokers were administered placebo and nicotine (2-mg lozenge). Brain activation to monetary reward anticipation and outcome was evaluated with functional magnetic resonance imaging. Relative to placebo, nicotine induced more NAcc reactivity to reward anticipation. Greater NAcc activation during anticipation was significantly associated with lower NAcc activation to outcome. During outcome, nicotine reduced NAcc functional connectivity with cortical regions including the anterior cingulate cortex, orbitofrontal cortex, and insula. These regions showed the same negative relationship between reward anticipation and outcome as noted in the NAcc. The current findings significantly improve our understanding of how nicotine changes corticostriatal circuit function and communication during distinct phases of reward processing and critically show that these alterations happen acutely following a single dose. The implications of this work explain nicotinic modulation of general reward function, which offer insights into the initial drive to smoke and the subsequent difficulty in cessation.

The Effect of Nicotine on Macular Microcirculation in Healthy Subjects.

To evaluate the acute effects of nicotine on macular microvasculature by optical coherence tomography angiography (OCTA). Non-smokers who were administered 4 mg nicotine gum (study group) or placebo gum (control group) were enrolled, 18 individuals in each group. All participants underwent OCTA at baseline and 1 hour after gum chewing. Macular flow area, macular vessel density, foveal avascular zone area, central foveal thickness, and subfoveal choroidal thickness were analyzed. Macular flow area, vessel density, and subfoveal choroidal thickness decreased in the nicotine group (P < .05). No statistically significant difference observed in central foveal thickness, when compared with baseline measurement (P > .05). Nicotine causes a significant decrease in macular microcirculation. Deterioration of macular microcirculation can be quantitatively detected by OCTA noninvasively. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:691-700.].

I wake up and hit the JUUL: Analyzing Twitter for JUUL nicotine effects and dependence

BackgroundJUUL—a novel electronic nicotine delivery system (ENDS)—comprises most of the ENDS market share. Additionally, JUUL has a high nicotine content and utilizes a patented nicotine salt formulation aimed to speed absorption. Many JUUL users are not aware of the nicotine content and therefore may not be expecting acute nicotine effects or potential for dependence. This study sought to analyze Twitter messages (“tweets”) regarding nicotine, symptoms of dependence, and withdrawal related to JUUL use. MethodsData were collected from Twitter’s Filtered Streams interface 4/11–6/16/2018 by retrieving tweets matching the terms “juul,” “juuls,” and “juuling” that also used words consistent with nicotine effects, symptoms of dependence, and withdrawal. A random 5% subsample (n = 1986) was coded by 2 independent coders. Cohen’s κ for inter-rater reliability ranged 0.62–1.00 for all coded variables. Tweets were assessed using a qualitative content analysis approach. ResultsA total of 335 tweets mentioned dependence-related themes, including use upon waking and compulsion to use. A total of 189 tweets mentioned themes related to nicotine, with almost 15% of these tweets describing physical effects. Additionally, 42 tweets mentioned themes related to quitting JUUL and/or withdrawal from JUUL. DiscussionThis qualitative analysis suggests that users of JUUL are experiencing symptoms of nicotine exposure and dependence. Considering the high nicotine content of JUUL and the rising popularity among young people, more research around initiation of and dependence on JUUL, as well as the impact of recent FDA policy changes, should be conducted.

Nicotinic Acetylcholine Receptor Density in the "Higher-Order" Thalamus Projecting to the Prefrontal Cortex in Humans: a PET Study.

The parcellation of the thalamus into different nuclei involved in different corticothalamocortical loops reflects its functional diversity. The connections between the mediodorsal nucleus and the prefrontal cortex play a major role in cognition, particularly in the rapid processing of behaviorally relevant information. The thalamus is the brain region with the highest density in α4β2 nicotinic acetylcholine receptors, the main human nicotinic acetylcholine receptor subtype. The aim of this study was to investigate the possible role of the nicotinic cholinergic system in the thalamo-cortical loops measuring receptor density in different subregions of the thalamus, based on their cortical connectivity. We studied α4β2 nicotinic acetylcholine receptors using positron emission tomography and [18F]Fluoro-A-85380, a radiotracer specific for this receptor subtype, in 36 non-smoking male subjects, including 12 healthy controls and 24 patients with epilepsy. [18F]Fluoro-A-85380 ratio index of binding potential was compared by a repeated measures general linear model, including the thalamic subregions and the brain hemisphere as within-subject factor and clinical groups as between-subject factor. The "prefrontal" thalamus, the subregion including the mediodorsal nucleus, had a significantly higher nicotinic acetylcholine receptor density than all other thalamic subregions. These findings were confirmed when analyzing solely the 12 healthy controls. This particular neurochemical organization of the thalamus supports a major role of the cholinergic system in the loops between the thalamus and the prefrontal cortex. The highest nicotinic acetylcholine receptor density in the « higher-order thalamus » could partly explain the beneficial effect of acute nicotine on attentional and executive functions and possibly the pathophysiology of some neuropsychiatric disorders.