Nicotine Intake Research Articles

Mifepristone decreases nicotine intake in dependent and non-dependent adult rats.

Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new treatments to reduce tobacco and nicotine use. Glucocorticoid receptor blockade shows promise as a novel treatment for drug abuse and stress-related disorders. These studies aim to investigate whether glucocorticoid receptor blockade with mifepristone diminishes the reinforcing properties of nicotine in rats with intermittent or daily long access to nicotine. The rats self-administered 0.06 mg/kg/inf of nicotine for 6 h per day, with either intermittent or daily access for 4 weeks before treatment with mifepristone. Daily nicotine self-administration models regular smoking, while intermittent nicotine self-administration models occasional smoking. To determine whether the rats were dependent, they were treated with the nicotinic acetylcholine receptor antagonist mecamylamine, and somatic signs were recorded. The rats with intermittent access to nicotine had a higher level of nicotine intake per session than those with daily access but only the rats with daily access to nicotine showed signs of physical dependence. Furthermore, mecamylamine increased nicotine intake during the first hour of access in rats with daily access but not in those with intermittent access. Mifepristone decreased total nicotine intake in rats with intermittent and daily access to nicotine. Moreover, mifepristone decreased the distance traveled and rearing in the open field test and operant responding for food pellets. These findings indicate that mifepristone decreases nicotine intake but this effect may be partially attributed to the sedative effects of mifepristone.

Intermittent nicotine access is as effective as continuous access in promoting nicotine seeking and taking in rats.

Nicotine is a principal psychoactive agent in tobacco, contributing to tobacco's addictive potential. Preclinical studies on the effects of voluntary nicotine intake typically use self-administration procedures that provide continuous nicotine access during each self-administration session. However, many smokers consume cigarettes intermittently rather than continuously throughout each day. For drugs including cocaine and opioids, research in laboratory rats shows that intermittent intake can be more effective than continuous intake in producing patterns of drug use relevant to addiction. We determined how intermittent versus continuous nicotine self-administration influences nicotine seeking and taking behaviours. Female and male rats had continuous (i.e., Long Access; LgA, 6h/day) or intermittent (IntA; 12min ON, 60min OFF, for 6h/day) access to intravenous nicotine (15µg/kg/infusion), for 12 daily sessions. We then assessed intake, responding for nicotine under a progressive ratio schedule of drug reinforcement and cue- and nicotine-induced reinstatement of drug seeking. We also estimated nicotine pharmacokinetic parameters during LgA and IntA self-administration. Overall, LgA rats took twice more nicotine than did IntA rats, yielding more sustained increases in estimated brain concentrations of the drug. However, the two groups showed similar motivation to seek and take nicotine, as measured using reinstatement and progressive ratio procedures, respectively. Intermittent nicotine use is just as effective as continuous use in producing addiction-relevant behaviours, despite significantly less nicotine exposure. This has implications for modeling nicotine self-administration patterns in human smokers and resulting effects on brain and behaviour.

Changes in biomarkers of exposure and withdrawal symptom among Chinese adult smokers after completely or partially switching from combustible cigarettes to an electronic nicotine delivery system.

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult smokers who were naive ENDS users. Forty-six subjects were randomized to 4 study groups (n = 11-12 per group): exclusive ENDS use, dual use of ENDS and cigarettes, exclusive cigarettes use, and smoking abstinence. Subjects were confined in clinic for 5 consecutive days and product use was ad libitum. Nicotine and its metabolites (cotinine and 3-hydroxycotinine), and BoEs (AAMA, CEMA, HEMA, HMPMA, 3-HPMA, SPMA, exhaled CO, and exhaled NO) were measured. Withdrawal symptom was measured using MNWS throughout the 5-day period. Six urine BoEs of volatile organic compounds decreased by 55.1-84.1% in the exclusive ENDS use group, which is similar to the smoking abstinence group (67.2-87.4%). The level of decrease was 56.8-70.4% in the dual use group and 10.7-39.0% in the cigarettes group. Urine total nicotine exposure had a non-significant increase in the exclusive ENDS use group, and plasma nicotine and cotinine showed a trend of increasing day by day. After completely or partially switching to ENDS use among Chinese smokers, exposure to selected toxicants were significantly decreased. The results of this study add to the body of evidence that exposure to toxic substance decreased among smokers after complete or partial switch from combustible cigarettes to ENDS use. As part of transition to experienced ENDS use, this study found that smokers of the initial stage who have no prior ENDS experience may increase nicotine intake after switching to ENDS use.

Neuronal Excitability in the Medial Habenula and Ventral Tegmental Area Is Differentially Modulated by Nicotine Dosage and Menthol in a Sex-Specific Manner.

The medial habenula (MHb) has been identified as the limiting factor for nicotine intake and facilitating nicotine withdrawal. However, few studies have assessed MHb neuronal excitability in response to nicotine, and, currently, a gap in knowledge is present for finding behavioral correlates to neuronal excitability in the region. Moreover, no study to date has evaluated sex or nicotine dosage as factors of excitability in the MHb. Here, we utilized an e-vape self-administration (EVSA) model to determine differences between sexes with different nicotine dosages ± menthol. Following this paradigm, we employed patch-clamp electrophysiology to assess key metrics of MHb neuronal excitability in relation to behavioral endpoints. We observed female mice self-administered significantly more than males, regardless of dosage. We also observed a direct correlation between self-administration behavior and MHb excitability with low-dose nicotine + menthol in males. Conversely, a high dose of nicotine ± menthol yields an inverse correlation between excitability and self-administration behavior in males only. In addition, intrinsic excitability in the ventral tegmental area (VTA) does not track with the amount of nicotine self-administered. Rather, they correlate to the active/inactive discrimination of mice. Using fast-scan cyclic voltammetry, we also observed that dopamine release dynamics are linked to reinforcement-related behavior in males and motivation-related behaviors in females. These results point to a sex-specific difference in the activity of the MHb and VTA leading to distinct differences in self-administration behavior. His could lend evidence to clinical observations of smoking and nicotine-use behavior differing between males and females.

Impact of the coronavirus (COVID-19) disease pandemic on healthy lifestyle behaviors in persons with and without disabilities in Qatar.

This study aimed to examine the impact of the COVID-19 pandemic on the lifestyle behaviors which included physical activity, sedentariness, healthy eating habits, sleep habits, and tobacco use in persons with and without disabilities in Qatar. This cross-sectional study used a structured, online questionnaire. The collected data included demographics, mental health, physical health, eating habits, body weight, sleep, and nicotine intake. This study was conducted between September 25, 2020, and December 31, 2020. Seventy respondents from Qatar participated in the study. Pre-pandemic healthy lifestyle behaviors (physical activity, healthy diet, sleep, etc.) showed no significant differences between people with and without disabilities. However, perceived changes in mental and physical health and eating habits during the pandemic lockdown differed between people with and without disabilities. People with disabilities reported worsening mental health (64.7%), physical health (53%), and dietary habits compared to the pre-pandemic levels. Furthermore, the more severe the disability, the more significant is its impact on mental and physical health. This study indicated that the pandemic has had a significant impact on the mental and physical health of people with and without disabilities in Qatar. These findings reveal how closely individuals with disabilities and their lifestyle choices are related to their mental and physical well-being. This will enable the development of specific interventions for similar situations in the future.

The effect of CNQX on self-administration: present in nicotine, absent in methamphetamine model.

Addiction is a chronic disease with limited pharmacological options for intervention. Focusing on reducing glutamate levels in the brain seems to be a promising strategy in addiction treatment research. Our research aimed to evaluate the effects of CNQX, an antagonist that targets AMPA and kainate glutamatergic receptors while also exhibiting affinity for the NMDA receptor, especially by modulating its glycine site. We conducted this assessment on the self-administration of nicotine and methamphetamine via intravenous (IV) administration in rats. An operant IV self-administration model was used in male Wistar rats. When animals maintained a stable intake of nicotine or methamphetamine, we administered a single injection of CNQX (in the dose of 3 or 6 mg/kg IV) to evaluate its effect on drug intake. Subsequently, the rats were forced to abstain by staying in their home cages for 2 weeks. The period of abstinence was followed by a context-induced relapse-like session before which animals were pretreated with the injection of CNQX (3 or 6 mg/kg IV) to evaluate its effect on drug seeking. CNQX significantly reduced nicotine intake during the maintenance phase, but no effect was revealed on nicotine seeking after forced abstinence. CNQX did not affect methamphetamine taking or seeking. The effect of reducing nicotine taking but not seeking could be explained by different involvement of glutamatergic receptors in various stages of nicotine dependence.

Effectiveness of pharmacotherapies for diabetes on nicotine, food, and water intake in insulin-resistant rats.

The intersectionality between diabetes medications and nicotine consumption was assessed in female and male rats. Briefly, the rats were fed a high-fat diet (HFD) or regular diet (RD) for 4weeks. Then separate groups received vehicle or a low dose of streptozotocin (STZ; 25mg/kg). Three days later, insulin resistance was assessed by measuring plasma glucose levels for 180min following an injection of insulin (0.75U/kg). The rats were then prepared with jugular catheters, and they were given 23h access to nicotine intravenous self-administration (IVSA) in 4days cycles with 3days of forced abstinence in their home cages where they consumed their respective diet. During the IVSA sessions, operant responses for food and water and changes in body weight were recorded. Prior to administration of the pharmacotherapies, the rats were given access to two doses of nicotine (0.015 then 0.03mg/kg for the remainder of the study). Then, daily injections of the pharmacotherapies were given at the onset of dark cycle (6p.m.) in the following order: 1) dapagliflozin (3.0 then 10.0mg/kg), 2) insulin (0.75U/kg twice), and 3) bromocriptine (3.0 then 10.0mg/kg). The results suggest that our HFD+STZ regiment induced insulin resistance in female and male rats. Also, the HFD-fed rats displayed higher nicotine intake than RD controls, regardless of sex. Administration of insulin, but not dapagliflozin or bromocriptine, normalized nicotine intake in HFD-fed rats to control levels. These results have clinical implications regarding the potential efficacy of insulin to control excessive nicotine intake in persons with diabetes.

Cannabidiol as a potential cessation therapeutic: Effects on intravenous nicotine self-administration and withdrawal symptoms in mice

Cigarette smoking remains a leading cause of preventable disease and death worldwide. Due to the devastating negative health effects of smoking, many users attempt to quit, but few are successful in the long-term. Thus, there is a critical need for novel therapeutic approaches. In these investigations, we sought to examine whether cannabidiol (CBD) has the potential to be repurposed as a nicotine cessation therapeutic. In the first study, male and female mice were trained to respond for intravenous nicotine infusions at either a low or moderate nicotine dose and then were pretreated with CBD prior to their drug-taking session. We found that CBD produced a significant decrease in the number of nicotine rewards earned, and this effect was evidenced across CBD doses and with both the low and moderate levels of nicotine intake. These effects on drug intake were not due to general motor-related effects, since mice self-administering food pellets did not alter their behavior with CBD administration. The potential effects of CBD in mitigating nicotine withdrawal symptoms were then investigated. We found that CBD attenuated the somatic signs of nicotine withdrawal and prevented nicotine's hyperalgesia-inducing effects. Taken together, these results demonstrate that modulation of cannabinoid signaling may be a viable therapeutic option as a smoking cessation aid.

Sex differences in nicotine intake and relapse behavior in nicotine-dependent adult wistar rats.

Tobacco use is highly addictive and the leading cause of premature mortality in the world. Long-access nicotine self-administration procedures in rats closely model human smoking behavior. However, significant gaps remain in our understanding of sex differences in the development of dependence and relapse in adult rats. In the present study, we investigated operant responding for both nicotine and saline and the development of dependence in adult rats of both sexes. The rats had daily access to nicotine or saline for 6h per day, 7days per week. Dependence was assessed by evaluating precipitated and spontaneous somatic withdrawal signs, measuring locomotor activity in the small open field test, and assessing anxiety-like behavior in the large open field and elevated plus maze test. The sucrose preference test was used to determine if cessation of nicotine intake leads to anhedonia. It was also investigated if a period of forced abstinence affects nicotine-seeking behavior. This study showed that nicotine intake is higher in females than in males when given daily long access to nicotine. Daily nicotine self-administration led to more precipitated and spontaneous somatic withdrawal signs compared to saline self-administration, with no sex differences observed. In addition, cessation of nicotine intake led to a similar increase in activity in both males and females in the small open field test. However, cessation of nicotine intake did not increase anxiety-like behavior or cause anhedonia in either males or females. A time course analysis revealed that the nicotinic acetylcholine receptor antagonist mecamylamine affected nicotine intake differently in males and females, increasing intake in males and decreasing intake in females. Three weeks of forced abstinence led to an increase in nicotine and saline-seeking behavior. The rats exhibited more nicotine than saline seeking, and the females displayed more nicotine seeking than the males. The present findings demonstrate that females self-administer more nicotine and display more nicotine-seeking behavior than males. Furthermore, there were no sex differences in somatic withdrawal signs or activity during abstinence from nicotine. This work underscores the importance of considering sex differences across various aspects of addiction, including intake and relapse, when developing novel treatments for tobacco use disorder.

Nicotine Addiction, Alcohol Use Disorder and Bipolar Disorder

Bipolar affective disorder has a wide range of effects on human health and is extremely harmful, and the mortality rate of patients continues to grow. Meanwhile, most people, especially those with mental illness, tend to numb themselves by smoking and drinking. Unfortunately, tobacco and alcohol abuse are also extremely harmful to human health, moreover, the cost of living will be increased due to addiction of these things. At the same time, the unconscious mind after using alcohol and tobacco has also brought great uneasiness to society, thus leading to increased burden on individuals and society. This review discusses the genetics, comorbidity, and treatment of nicotine dependence, alcohol use disorder, and bipolar disorder, and finds that the severity of bipolar disorder patients is positively correlated with the severity of alcohol use disorder and nicotine dependence. Both patients with bipolar disorder and alcohol use disorder exhibit mutations in the BDNF gene, and an age peak in bipolar disorder coincides with a peak in nicotine dependence. In the end, it is believed that the interaction between comorbidities may become a breakthrough in the diagnosis or treatment of bipolar disorder in the future, and the easy-to-observe alcohol and nicotine intake can be used to assist in judging the current state of patients.

Adolescent restraint stress enhances adult nicotine reinforcement in male and female rats

Adolescent stress is a risk factor for the initiation of nicotine use, but whether adolescent stress can enhance nicotine reinforcement when it is initiated later in adulthood is unknown, and it is unclear whether males and females are equally impacted. Therefore, this study assessed physiological responses (body weight and blood serum corticosterone – CORT) to restraint stress (RS) during adolescence (P28–55) or during adulthood (P70–96) in male and female Sprague-Dawley rats. When all subjects reached adulthood (P69 or 110; 2 weeks after termination of stress exposure), they were tested on sucrose preference and intravenous single-dose nicotine (0.03 mg/kg/infusion) self-administration. It was found that all rats displayed a significant CORT response to RS. Importantly, stress during adolescence, but not during adulthood, enhanced subsequent acquisition of nicotine intake tested in adulthood. Although this effect was observed in both sexes, only males displayed reduced body weight gain and adult sucrose preference. Moreover, regardless of stress exposure, females were more stimulated by nicotine, consumed more nicotine overall, and displayed enhanced nicotine seeking. These results suggest that adolescence is a period of heightened sensitivity to the enhancing effect of repeated stress on the susceptibility to develop nicotine dependence later in life in both sexes.

E-cigarette aerosol exposure effect on bone biomechanical properties in murine models

Numerous studies have shown the detrimental health effects of tobacco smoking on bone volume and strength in human and animal models. Little is known regarding the impacts of e-cigarettes, a form of smoke-less nicotine intake, despite their growing population of users. This study uses murine models to evaluate the effects of exposure to e-cigarette aerosols (JUUL) on bone structure and strength through micro-CT imaging and mechanical testing. JUUL mice had more trabecular bone in thickness and volume, yet lower ultimate stress and modulus values in the cortical bone than the control mice. These outcomes suggest that, although vaping can result in a higher bone volume, this bone is weaker than average. E-cigarettes should be examined more closely regarding adolescence and long-term consequences on skeletal health.

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.

Accelerated epigenetic age, inflammation, and gene expression in lung: comparisons of smokers and vapers with non-smokers

BackgroundCigarette smoking and aging are the main risk factors for pulmonary diseases, including cancer. Epigenetic aging may explain the relationship between smoking, electronic cigarette vaping, and pulmonary health. No study has examined smoking and vaping-related epigenetic aging in relation to lung biomarkers.MethodsLung epigenetic aging measured by DNA methylation (mAge) and its acceleration (mAA) was assessed in young (age 21–30) electronic cigarette vapers (EC, n = 14, including 3 never-smoking EC), smokers (SM, n = 16), and non-EC/non-SM (NS, n = 39). We investigated relationships of mAge estimates with chronological age (Horvath-mAge), lifespan/mortality (Grim-mAge), telomere length (TL-mAge), smoking/EC history, urinary biomarkers, lung cytokines, and transcriptome.ResultsCompared to NS, EC and SM had significantly older Grim-mAge, shorter TL-mAge, significantly accelerated Grim-mAge and decelerated TL-mAge. Among SM, Grim-mAA was associated with nicotine intake and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). For EC, Horvath-mAA was significantly correlated with puffs per day. Overall, cytokines (IL-1β, IL-6, and IL-8) and 759 transcripts (651 unique genes) were significantly associated with Grim-mAA. Grim-mAA-associated genes were highly enriched in immune-related pathways and genes that play a role in the morphology and structures of cells/tissues.ConclusionsFaster lung mAge for SM is consistent with prior studies of blood. Faster lung mAge for EC compared to NS indicates possible adverse pulmonary effects of EC on biological aging. Our findings support further research, particularly on epigenetic markers, on effects of smoking and vaping on pulmonary health. Given that most EC are former smokers, further study is needed to understand unique effects of electronic cigarettes on biological aging.

Ovarian toxicity of e-cigarette liquids: Effects of components and high and low nicotine concentration e-cigarette liquid in vitro.

Electronic cigarette use has become increasingly popular, with potential consequences for reproductive health. We aimed to investigate the effects of different components of e-liquid on the ovary and compare the impact of low nicotine concentration e-liquids (LN e-liquids) and high nicotine concentration e-liquids (HN e-liquids) on ovarian toxicity. A total of 378 rat ovaries were divided into seven groups, including control (no intervention), nicotine (0.05 mg/mL), flavoring (0.25 μL/mL), propylene glycol (PG) (2.5 μL/mL), vegetable glycerin (VG) (2.0 μL/mL), LN e-liquid (0.05 mg nicotine + 0.25 μL flavoring + 2.5 μL PG + 2.0 μL VG + 0.25 μL distilled water/mL medium) and HN e-liquid groups (0.05 mg nicotine + 0.05 μL flavoring + 0.5 μL PG + 0.4 μL VG + 0.05 μL distilled water/mL medium). After three hours of in vitro culture, ovarian morphology, oxidation levels [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA)], and apoptosis levels [factor related apoptosis (Fas), Cyt-c, Caspase-9, Caspase-3] were analyzed. Our findings indicate that nicotine has limited impact on the ovary, while flavoring, PG, and VG all cause ovarian damage including morphological damage, disruption of oxidative balance and promotion of apoptosis, with VG having the most significant effect. Moreover, LN e-liquids may lead to more severe ovarian damage than HN e-liquids at an equal intake of total nicotine. Our study highlights that in e-liquid formula, nicotine has a limited effect on the ovaries, but flavoring, PG, and VG all cause damage to the ovaries, with VG the most damaging. At a consistent level of total nicotine intake, e-liquids with low nicotine concentrations cause more damage to the ovaries than those with high nicotine concentrations. These findings contribute to a better understanding of the impact of e-liquids on ovarian health and have important implications for public health policy.

Exercise Effects on Health-Related Quality of Life (HRQOL), Muscular Function, Cardiorespiratory Function, and Body Composition in Smokers: A Narrative Review.

Smoking is amongst the leading global threats with high incidences of preventable premature mortality, morbidity, and various chronic diseases. The World Health Organization (WHO) proclaims a decrease in the prevalence of daily smoking in both males and females from 1980 to 2012, however, the number of regular smokers since then has exponentially increased. The low socio-income status individuals contribute greatly towards tobacco-attributable diseases due to limited access to healthcare systems, mostly in developing countries as compared to developed countries. Smoking affects the optimal functioning of the human body, which results in altered body system processes. Although a high intake of nicotine can lead to prolonged adherence and dependence on smoking, other factors, such as an individual's level of health-related quality of life (HRQOL), stress, depression, and anxiety, can produce similar effects. Smoking has a wide impact on lifestyle factors, which explains the increase in the number of sedentary smokers with decreased health fitness levels and poor lifestyle conditions. Therefore, this study seeks to investigate the exercise effects on health-related quality of life (HRQOL), muscular function, cardiorespiratory function, and body composition in smokers. Concurrently, exercise as an intervention has been sourced as a rehabilitation strategy during smoking cessation programmes to restore the diminishing health components, however, a high rate of relapse occurs due to intolerable withdrawal symptoms.

Substitutability of nicotine and sucrose in rats: A behavioral economic analysis

Despite considerable evidence suggesting that sweet foods are a substitute for nicotine in humans, no formal behavioral economic analysis of this interrelationship has been conducted in nonhumans. The purpose of the present study was to examine this phenomenon in rats using concurrent schedules of sucrose pellet, chow pellet, and nicotine reinforcer delivery. Rats responded on separate levers that delivered sucrose pellets, chow pellets, or nicotine infusions under concurrent fixed-ratio (FR) 1 schedules for each commodity within a closed economy. Following stable food and nicotine intake, the unit price of either sucrose or nicotine (the primary commodity) was increased while the two alternative commodities remained unchanged. Substitution was quantified using a behavioral economic cross-price model, as well as a novel commodity relation index that normalizes consumption of dissimilar commodities. Asymmetrical partial substitution was observed, wherein sucrose served as a partial substitute for nicotine, but nicotine failed to substitute for sucrose. Moreover, sucrose was a stronger partial substitute for nicotine than chow in most rats. These findings indicate that substitution of food for nicotine depends on the type of food. These findings mirror the selective increase in carbohydrate intake that can occur during smoking cessation and demonstrate a behavioral economic mechanism that may mediate it.

Experimenter administered Δ9-THC decreases nicotine self-administration in a rat model

BackgroundThe co-use of nicotine and cannabis has been steadily rising in the United States. Rodent studies suggest that delta-9-tetrahydrocannabinol (THC) could increase addictive qualities of nicotine, but whether repeated THC exposure alters self-administration of nicotine has not been tested. We hypothesized that THC would increase the reinforcing effects of nicotine and alter nicotine intake. MethodsAdult male and female Sprague-Dawley rats were treated with THC (0, 3, 30 mg/kg) daily for 14 days prior to and during training for intravenous self-administration of nicotine. Rats were allowed to self-administer nicotine for several weeks, then tested for sensitivity to nicotine dose through multiple determinations of a nicotine dose-effect curve with or without THC pretreatment. A separate set of rats were trained on fixed ratio responding for sucrose and assessed for THC effects on behavior. ResultsPost-session THC decreased nicotine self-administration in male and female rats throughout acquisition and maintenance and increased the latency to stable rates of nicotine intake during acquisition. Post-session THC shifted nicotine dose-effect curves downward, and pre-session THC suppressed responding at higher nicotine doses. Unlike nicotine, responding for sucrose was not affected by post-session THC. Pre-session THC decreased responding for sucrose, particularly for THC-naïve rats. ConclusionsRepeated post-session THC decreased nicotine-taking behaviors but did not alter sucrose responding. Thus, post-session THC may alter sensitivity to nicotine. Pre-session THC treatment decreased lever pressing in both sucrose and nicotine studies, indicating this effect was nonspecific. These studies show that THC modulates patterns of nicotine intake in rat models.

Black Seed (<i>Nigella sativa</i>) oil restores smoke or nicotine-induced vascular impairment via improvement in endothelium-dependent relaxation: role of nitric oxide synthase and voltage-sensitive potassium channels

Background: Despite the overwhelming evidence linking smoking and nicotine intake with vascular function impairments, the mechanisms involved and the possible ameliorative effect of black seed (Nigella sativa (NS)) oil administration are not clearly understood. This study sought to determine the involvement of nitric oxide synthase and voltage-sensitive potassium channels in the modulation of vascular reactivity in cigarette or nicotine-exposed rats treated with NS oil.
 Methods: Thirty male Sprague-Dawley rats were divided into 6 groups comprising vehicle control (Control), NS oil only (NS), Smoke only (SMK), Smoke + NS oil (SMKNS), Nicotine only (NCT) and Nicotine + NS oil (NCTNS). Animals were either passively exposed to cigarette smoke or nicotine vapour for 12 weeks, however, NS oil treatment commenced from 9th-12th week orally. At the end of the 12-week experimental period, vascular reactivity to norepinephrine (NE), acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed with or without the presence of L-nitro-arginine (LNA) or 4-Amino-pyridine (4AP).
 Results: Percent contractile response to NE was higher (p < 0.01) while relaxation response to ACh was lower in the SMK and NCT (p < 0.05) groups. LNA-induced inhibition to ACh was significantly reduced in both SMK and NCT groups. 4AP-induced inhibition to ACh was significantly increased only in the NCT group. 4AP-induced inhibition to SNP was increased in SMK group. NS oil reduced only contractile response to NE in NCT group. It also significantly improved relaxation response to ACh as well as restored LNA-induced inhibition to ACh in the SMK and NCT groups. Interestingly, while NS oil reduced 4AP-induced inhibition in the NCT group, it reduced 4AP-induced inhibition to SNP in the SMK group.
 Conclusion: NS oil ameliorates vascular dysfunction by reducing contractile response in rats exposed to nicotine vapour while increasing endothelium-dependent relaxation as well as restoring differentially both LNA- and 4AP-induced inhibition in rats exposed to cigarette smoke and nicotine vapour.

The Impact of High or Low Doses of Nicotine in a Mouse Model of Vapor Self-Administration.

A wide variety of nicotine concentrations and formulations are available to users of electronic nicotine delivery systems (ENDS). This is increasingly true when considering the many flavors available with ENDS products. To date, there have been few preclinical investigations into the impact of nicotine doses, with and without flavors, on vaping-related behaviors. This present study evaluated how nicotine concentrations relevant to tank-based and pod-based ENDS, with and without flavors, impact reinforcement-related behavior in a mouse model. Adult male and female C57/BL6J mice were used in vapor-inhalation self-administration assays. Mice were assigned e-liquids containing 6 mg/mL or 60 mg/mL nicotine. Additional mice were assigned these nicotine doses with green apple or menthol flavorants. Mice were trained on fixed-ratio 1 for 10, 2-hour sessions, then five sessions at FR3, three progressive ratio sessions, and two FR3 sessions. We observed male mice exhibited higher reinforcement-related behavior to menthol-flavored 6 mg/mL nicotine when compared to female mice. Males were only observed to have a menthol-induced enhancement of self-administration at 6 mg/mL nicotine and not 60 mg/mL nicotine. However, female mice exhibited significant menthol-induced increases in reinforcement-related behaviors with 60 mg/mL nicotine. These data provide evidence that males and females exhibit different dose sensitivities to nicotine. These sex-dependent differences in nicotine sensitivity also indicate that flavor-induced enhancement in nicotine intake is dependent on the different doses for each sex. There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our current study may support prior investigations that suggest flavors enhance the palatability of nicotine-containing products. However, this current study provides evidence that males and females exhibit different sensitivities to nicotine.