Exposure to smoke from high- but not low-nicotine cigarettes leads to signs of dependence in male rats and potentiates the effects of nicotine in female rats.
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ABSTRACT:
SUBMITTER: Chellian R
PROVIDER: S-EPMC7415730 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Most people start experimenting with tobacco products or e-cigarettes in early adolescence and become habitual smokers in late adolescence or adulthood. These studies investigated if exposure to tobacco smoke or nicotine during early and mid-adolescence affects nicotine intake in late adolescence and early adulthood. Male and female rats were exposed to tobacco smoke from low- and high-nicotine SPECTRUM cigarettes or nicotine (0.3 mg/kg, twice a day) from postnatal day (P) 24-42. The self-administration sessions started at P55. The rats self-administered nicotine for 14-15 days under a fixed-ratio 1 schedule, and on the first day, the maximum number of infusions was twenty. Exposure to smoke from high, but not low, nicotine cigarettes during adolescence increased nicotine self-administration in female but not male rats. Adolescent treatment with nicotine facilitated nicotine self-administration. On the first day of nicotine self-administration, nicotine-treated rats reached the maximum number of infusions before the saline-treated control rats. Nicotine intake was also higher in the nicotine-treated female rats than in the saline-treated females. There was no sex difference in nicotine intake in controls when the data from the studies were combined. Smoke exposure led to a dose-dependent increase in plasma nicotine and cotinine levels in adolescent rats. Exposure to smoke from high-nicotine cigarettes and 0.3 mg/kg of nicotine led to plasma nicotine and cotinine levels that are similar to those in tobacco users. These findings indicate that in females, but not males, exposure to nicotine during adolescence may facilitate smoking and e-cigarette use later in life.
| S-EPMC7660018 | biostudies-literature
Project description: Not available
| S-EPMC1569994 | biostudies-literature
Project description:IntroductionThe kappa-opioid receptor (KOR) has been implicated in mediating the behavioral and biochemical effects associated with nicotine reward and withdrawal; however, its underlying mechanisms remain to be further explored.MethodsAdult male Sprague-Dawley rats were used to establish a nicotine dependence and withdrawal model by injecting nicotine (3 mg/kg/day, s.c.) or vehicle for 14 days, followed by the termination of nicotine for 7 days. Body weight gain, pain behaviors, and withdrawal scores were assessed in succession. MicroRNA (miRNA) sequencing was performed, and quantitative real-time PCR was used to detect the expression of candidate miRNAs and Oprk1. Western blotting was performed to examine KOR protein expression of KOR. Luciferase assay was conducted to validate the relationship of certain miRNAs/Oprk1.ResultsThe behavioral results showed that nicotine dependence and withdrawal induced behavioral changes. Biochemical analyses demonstrated that miR-144-3p expression decreased and Oprk1/KOR expression increased in the prefrontal cortex, nucleus accumben, and hippocampus. Further investigation suggested that miR-144-3p exerted an inhibitory effect on Oprk1 expression in PC12 cells.ConclusionsThis study revealed that miR-144-3p/Oprk1/KOR might be a potential pathway underlying the adverse effects induced by nicotine dependence and withdrawal, and might provide a novel therapeutic target for smoking cessation.ImplicationsThis study demonstrates an impact of nicotine dependence and nicotine withdrawal on behavioral outcomes and the expressions of miR-144-3p/Oprk1/KOR in male rats. These findings have important translational implications given the continued use of nicotine and the difficulty in smoking cessation worldwide, which can be applied to alleviated the adverse effects induced by nicotine dependence and withdrawal, thus assist smokers to quit smoking.
| S-EPMC10664084 | biostudies-literature
Project description:IntroductionIn a sample of dual users of cigarettes and electronic nicotine delivery systems (ENDS; e-cigarettes), we evaluated psychometric properties of ENDS versions of the Nicotine Dependence Syndrome Scale (NDSS), the brief Wisconsin Inventory of Smoking Dependence Motives (WISDM), and the Fagerström Test for Nicotine Dependence (FTND). Using the NDSS, we tested the hypothesis that there would be one common underlying factor of dependence across the cigarette and ENDS scales and other product-specific factors.Aims and methodsAdult dual users (N = 404) completed baseline cigarette and ENDS versions of the NDSS, WISDM, and FTND, and biweekly surveys of their smoking and vaping. Analyses included bifactor modeling, which helps to identify both a general and product-specific factor for each item, and exploratory factor analyses of the combined cigarette and ENDS NDSS items and examinations of concurrent and predictive validity.ResultsThe bifactor model was not a good fit, suggesting the lack of one common underlying dependence factor. Factor analyses revealed separate, similar factors for both products, with only one factor (priority) showing overlap of cigarette and ENDS items. ENDS scales significantly predicted ENDS use over time, but not cigarette use. Cigarette scales did not predict ENDS use over time.ConclusionsAlthough the cigarette and ENDS NDSS versions showed similar factor structure, there was not a primary common underlying factor reflecting drive or tolerance, but rather product-specific factors. The cigarette scales were not valid for predicting ENDS use. These results highlight the importance of separately assessing dependence for cigarettes and ENDS in dual users.ImplicationsAlthough underlying dimensions of nicotine dependence may be similar for ENDS and cigarettes, separate, product-specific measures may be needed to understand differences in product-specific dependency and predict changes in use of each product over time.
| S-EPMC7976930 | biostudies-literature
Project description:The Food and Drug Administration has the authority to regulate tobacco product constituents, including nicotine, to promote public health. Reducing the nicotine content in cigarettes may lead to lower levels of addiction. Smokers however may compensate by smoking more cigarettes and/or smoking more intensely. The objective of this study was to test whether individual differences in the level of nicotine dependence (as measured by the Fagerstrom Test of Cigarette Dependence [FTCD]) and/or the rate of nicotine metabolism influence smoking behavior and exposure to tobacco toxicants when smokers are switched to reduced nicotine content cigarettes (RNC).Data from 51 participants from a previously published clinical trial of RNC were analyzed. Nicotine content of cigarettes was progressively reduced over 6 months and measures of smoking behavior, as well as nicotine metabolites and tobacco smoke toxicant exposure, CYP2A6 and nicotinic CHRNA5-A3-B4 (rs1051730) genotype were measured.Higher baseline FTCD predicted smoking more cigarettes per day (CPD), higher cotinine and smoke toxicant levels while smoking RNC throughout the study, with no interaction by RNC level. Time to first cigarette (TFC) was associated with differences in compensation. TFC within 10 min was associated with a greater increase in CPD compared to TFC greater than 10 min. Neither rate of nicotine metabolism, nor CYP2A6 or nicotinic receptor genotype, had an effect on the outcome variables of interest.FTCD is associated with overall exposure to nicotine and other constituents of tobacco smoke, while a short TFC is associated with an increased compensatory response after switching to RNC.
| S-EPMC4542742 | biostudies-literature
Project description:PurposeTo estimate the prevalence, patterns, and correlates of self-reported nicotine dependence symptoms among U.S. youth who use JUUL - a widely-sold e-cigarette brand - in 2019 and compare findings to nicotine dependence symptoms in youth who smoke cigarettes.MethodsData were from a nationally-representative subsample of 8th, 10th, and 12th grade students in the Monitoring the Future Study who had used JUUL or cigarettes in the past 30 days. Participants self-reported presence/absence of 9 different nicotine dependence symptoms for JUUL or cigarettes. Weighted percentages for JUUL or cigarette nicotine dependence symptom status (≥1 vs. 0 symptoms) and severity (count, range: 0-9) were calculated. Among JUUL users, we estimated associations of sociodemographic characteristics and other substance use with nicotine dependence and severity.ResultsAmong 1,748 past 30-day JUUL users, 41.3 % screened positive for ≥1 nicotine dependence symptoms; the mean symptom count was 1.6 (SD = 2.6). Non-nicotine substance use and more frequent JUUL use was associated with significantly greater odds of dependence and more severe dependence symptoms in multivariable models. The severity distribution of most (craving) and least (inability to quit) dependence symptom types observed in JUUL dependence paralleled those observed in analysis of combustible cigarette dependence symptoms in past 30-day smokers.ConclusionA substantial proportion of U.S. adolescent JUUL users reported symptoms of nicotine dependence, which is greater for those who vape more frequently and use other substances. Nicotine dependence screening, prevention, and regulatory policies addressing use of JUUL or similar e-cigarette products should be considered to protect U.S. youth.
| S-EPMC8464491 | biostudies-literature
Project description:BackgroundCo-use of tobacco and cannabis and dual use of cigarettes and e-cigarettes are very common among young adults. However, it is unclear whether co-use of cigarettes, e-cigarettes, and/or cannabis is associated with higher levels of nicotine dependence than cigarette-only use. We investigated the relationship between cigarette/nicotine dependence and co-use of tobacco and cannabis among 4 groups of cigarette smokers aged 18-35: cigarette-only smokers, cigarette-e-cigarette (CIG-ECIG) co-users, cigarette-cannabis (CIG-CAN) co-users, and cigarette-e-cigarette-cannabis (CIG-ECIG-CAN) co-users.MethodsData were from a 2018 cross-sectional survey based on a national convenience sample of smokers aged 18-35 (n = 315). Cigarette/nicotine dependence was measured by the Fagerstrom Test of Nicotine Dependence (FTND) and e-cigarette dependence was measured by the Penn State E-cigarette Dependence Index. Bivariate analyses examined sociodemographic and tobacco/other substance use characteristics by co-use status and multivariable linear regression assessed the relationship between co-use and nicotine dependence.ResultsIn the sample, 27.6% were cigarette-only smokers, 24.8% were CIG-ECIG, 27.6% were CIG-CAN, and 20.0% were CIG-ECIG-CAN co-users. Significant differences were observed in sociodemographic and tobacco/other substance use characteristics by co-use status. E-cigarette co-users had low e-cigarette dependence, but moderate FTND scores. In adjusted analyses, only CIG-ECIG co-use was associated with higher FTND scores compared to cigarette-only smoking. However, CIG-ECIG and CIG-ECIG-CAN co-use were associated with higher FTND scores compared to CIG-CAN co-use.ConclusionsCo-use of cigarettes and e-cigarettes was associated with greater nicotine dependence among smokers aged 18-35. Additional research is needed to understand the underlying mechanisms of these relationships and inform prevention efforts.
| S-EPMC10249428 | biostudies-literature
Project description:ImportanceMenthol may make cigarette smoke less aversive and could lead youth to smoke more frequently and become more dependent on nicotine.ObjectiveTo assess the association of menthol use with cigarette smoking frequency and nicotine dependence (ND) among youth cigarettes users.Design, setting, and participantsThis cohort study used a pooled sample of cohorts of US youth (aged 12-17 years at their baseline and follow-up interviews) in the Population Assessment of Tobacco and Health Study (September 2013 to November 2019). Household interviews were conducted using audio computer-assisted self-interviews. US youth who were past-30-day cigarette smokers at any of wave 2 through wave 5, completed the preceding survey (eg, wave 2 past-30-day cigarette smokers completed wave 1), and indicated whether they used menthol cigarettes were eligible. The association of menthol use with smoking frequency and ND was estimated using inverse probability of treatment weighting adjusted mean differences (aMDs), adjusted risk ratios (aRRs), and corresponding 95% CIs. Data were analyzed from December 2021 to March 2022.ExposuresMenthol use and transitions in use (switching to or from menthol cigarettes).Main outcomes and measuresMain outcomes were the number of days smoked in the past 30 days, the risk of frequent smoking (smoking ≥20 days in the past 30 days), and symptoms of ND.ResultsThere were a total of 1492 observations among 1096 US youth cigarette smokers, of whom 49.4% were female, 67.2% were non-Hispanic White, and 28.7% were aged 12 to 14 years at their baseline survey (all percentages are weighted). Among those who switched from not smoking to smoking (61% of the sample), menthol use was associated with smoking on 3.1 additional days (aMD; 95% CI, 1.9 to 4.2 days), 59% higher risk of being a frequent smoker (aRR, 1.59; 95% CI, 1.23 to 2.06), and 10% higher ND scores (aMD, 1.09; 95% CI, 1.02 to 1.17). Switching from smoking menthol to smoking nonmenthol (vs maintaining menthol use) was associated with smoking on 3.6 fewer days (aMD; 95% CI, -6.3 to -0.9 days) and 47% lower risk of being a frequent smoker (aRR, 0.68; 95% CI, 0.50 to 0.92).Conclusions and relevanceThese findings suggest that the addition of menthol to cigarettes is associated with increased smoking frequency and ND among US youth.
| S-EPMC9171563 | biostudies-literature
Project description:IntroductionMany people incorrectly think that very low nicotine content (VLNC) cigarettes are less carcinogenic than current cigarettes. This risk misperception by people who smoke could reduce motivation to quit under a nicotine reduction policy. We qualitatively examined perspectives on campaign messages designed to reduce misperceptions.Aims and methodsAdults who smoke from North Carolina participated in online interviews. After being introduced to the idea of a VLNC policy, participants were shown VLNC messages and asked about their perceptions on the clarity, understandability, persuasiveness, and meaning of the messages. We conducted a thematic content analysis of the transcripts.ResultsThirty adults who smoke cigarettes participated (15 females, 13 males, 2 nonbinary) with a mean age of 43 years. Central themes that emerged were: (1) Confusion about the proposed VLNC cigarette policy affected how messages were interpreted; (2) Messages that promote self-efficacy for quitting rather than guilt or fear were better received; and (3) Direct and succinct messages were seen as more able to grab attention and inform people who smoke. Some participant concerns focused on whether VLNC cigarettes would relieve their nicotine cravings and whether they would need to smoke more VLNC cigarettes to feel satisfied.ConclusionCampaign messages to educate the public about the harmful effects of smoking VLNC cigarettes may be more effective if people who smoke are informed about the policy's rationale to understand why nicotine is removed rather than the other harmful chemicals. Messages should also acknowledge the difficulty of quitting and be short and direct to capture attention.ImplicationsAdults who smoke have some confusion about nicotine reduction in cigarettes and this affects how they perceive potential communication campaign messages about the risk of smoking VLNC cigarettes. In our qualitative research, we found that adults who smoke prefer messages about VLNC cigarettes that acknowledge the challenge of quitting and that are direct and succinct. With further development, campaign messages may be able to reduce misperceptions about VLNC cigarettes and maximize the public health benefit of a nicotine reduction policy.
| S-EPMC9653078 | biostudies-literature
Project description:Previous research has established sex differences associated with nicotine intake, however a significant gap in knowledge remains regarding the molecular mechanisms that govern these differences at the transcriptional level. One critical regulator of transcription are microRNAs (miRNAs). miRNAs are a family of non-coding RNAs that regulate an array of important biological functions altered in several disease states, including neuroadaptive changes within the brain associated with drug dependence. We examined the prefrontal cortex (PFC) from male and female Sprague-Dawley rats following self-administration (22 days) of nicotine or yoked saline controls using next generation RNA-Sequencing (RNA-Seq) technology and found an array of miRNAs to be significantly and differentially regulated by nicotine self-administration. Of these, we found the expression of miR-199a and 214, which are expressed on the same cluster of chromosome 1, to be upregulated in the female rats exposed to nicotine; upregulation in this group was further validated by real time polymerase chain reaction (RT-PCR). Bioinformatics analysis to assess common targets of miR-199/214 identified Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)- dependent deacetylase that plays a role in apoptosis, neuron survival, and stress resistance. Using western-blot, we confirmed downregulation of SIRT1 and increased cleaved caspase 3 expression in the brains of nicotine-exposed female rats and no change in expression levels in the other groups. Collectively, our findings highlight a miR-199/214 regulatory network that, through SIRT1, may be associated with nicotine seeking in females which may serve as a potential therapeutic target for sex-specific treatment approaches.
| S-EPMC6269448 | biostudies-literature