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Current Neuropharmacology 2018Cigarette smoking is the main cause of preventable death in developed countries. While the direct positive behavioral reinforcing effect of nicotine has historically... (Review)
Review
BACKGROUND
Cigarette smoking is the main cause of preventable death in developed countries. While the direct positive behavioral reinforcing effect of nicotine has historically been considered the primary mechanism driving the development of TUD, accumulating contemporary research suggests that the cognitive-enhancing effects of nicotine may also significantly contribute to the initiation and maintenance of TUD, especially in individuals with pre-existing cognitive deficits.
METHODS
We provide a selective overview of recent advances in understanding nicotine's effects on cognitive function, a discussion of the role of cognitive function in vulnerability to TUD, followed by an overview of the neurobiological mechanisms underlying the cognitive effects of nicotine.
RESULTS
Preclinical models and human studies have demonstrated that nicotine has cognitiveenhancing effects. Attention, working memory, fine motor skills and episodic memory functions are particularly sensitive to nicotine's effects. Recent studies have demonstrated that the α4, β2, and α7 subunits of the nicotinic acetylcholine receptor (nAChR) participate in the cognitive-enhancing effects of nicotine. Imaging studies have been instrumental in identifying brain regions where nicotine is active, and research on the dynamics of large-scale networks after activation by, or withdrawal from, nicotine hold promise for improved understanding of the complex actions of nicotine on human cognition.
CONCLUSION
Because poor cognitive performance at baseline predicts relapse among smokers who are attempting to quit smoking, studies examining the potential efficacy of cognitive-enhancement as strategy for the treatment of TUD may lead to the development of more efficacious interventions.
Topics: Animals; Cognition; Humans; Nicotine; Nicotinic Agonists; Tobacco Use Disorder
PubMed: 29110618
DOI: 10.2174/1570159X15666171103152136 -
Nature Reviews. Cardiology Aug 2017Cardiovascular safety is an important consideration in the debate on the benefits versus the risks of electronic cigarette (EC) use. EC emissions that might have adverse... (Review)
Review
Cardiovascular safety is an important consideration in the debate on the benefits versus the risks of electronic cigarette (EC) use. EC emissions that might have adverse effects on cardiovascular health include nicotine, oxidants, aldehydes, particulates, and flavourants. To date, most of the cardiovascular effects of ECs demonstrated in humans are consistent with the known effects of nicotine. Pharmacological and toxicological studies support the biological plausibility that nicotine contributes to acute cardiovascular events and accelerated atherogenesis. However, epidemiological studies assessing Swedish smokeless tobacco, which exposes users to nicotine without combustion products, generally have not found an increased risk of myocardial infarction or stroke among users, but suggest that nicotine might contribute to acute cardiovascular events, especially in those with underlying coronary heart disease. The effects of aldehydes, particulates, and flavourants derived from ECs on cardiovascular health have not been determined. Although ECs might pose some cardiovascular risk to users, particularly those with existing cardiovascular disease, the risk is thought to be less than that of cigarette smoking based on qualitative and quantitative comparisons of EC aerosol versus cigarette smoke constituents. The adoption of ECs rather than cigarette smoking might, therefore, result in an overall benefit for public health.
Topics: Cardiovascular Diseases; Cardiovascular System; Consumer Product Safety; Electronic Nicotine Delivery Systems; Humans; Nicotine; Smoking; Tobacco Smoking
PubMed: 28332500
DOI: 10.1038/nrcardio.2017.36 -
Neuropharmacology Oct 2020Nicotine is a highly addictive drug found in tobacco that drives its continued use despite the harmful consequences. The initiation of nicotine abuse involves the... (Review)
Review
Nicotine is a highly addictive drug found in tobacco that drives its continued use despite the harmful consequences. The initiation of nicotine abuse involves the mesolimbic dopamine system, which contributes to the rewarding sensory stimuli and associative learning processes in the beginning stages of addiction. Nicotine binds to neuronal nicotinic acetylcholine receptors (nAChRs), which come in a diverse collection of subtypes. The nAChRs that contain the α4 and β2 subunits, often in combination with the α6 subunit, are particularly important for nicotine's ability to increase midbrain dopamine neuron firing rates and phasic burst firing. Chronic nicotine exposure results in numerous neuroadaptations, including the upregulation of particular nAChR subtypes associated with long-term desensitization of the receptors. When nicotine is no longer present, for example during attempts to quit smoking, a withdrawal syndrome develops. The expression of physical withdrawal symptoms depends mainly on the α2, α3, α5, and β4 nicotinic subunits in the epithalamic habenular complex and its target regions. Thus, nicotine affects diverse neural systems and an array of nAChR subtypes to mediate the overall addiction process. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.
Topics: Animals; Brain; Humans; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Protein Subunits; Receptors, Nicotinic; Tobacco Use Disorder
PubMed: 32738308
DOI: 10.1016/j.neuropharm.2020.108256 -
The Journal of Physiology Nov 2020Tobacco smoking is highly addictive and causes respiratory disease, cardiovascular disease and multiple types of cancer. Electronic-cigarettes (e-cigarettes) are... (Review)
Review
Tobacco smoking is highly addictive and causes respiratory disease, cardiovascular disease and multiple types of cancer. Electronic-cigarettes (e-cigarettes) are non-combustible tobacco alternatives that aerosolize nicotine and flavouring agents in a propylene glycol-vegetable glycerine vehicle. They were originally envisaged as a tobacco cessation aid, but whether or not they help people to quit tobacco use is controversial. In this review, we have compared and contrasted what is known regarding the effects of nicotine on the lungs vs. the effects of nicotine in the brain in the context of addiction. Critically, both combustible tobacco products and e-cigarettes contain nicotine, a highly addictive, plant-derived alkaloid that binds to nicotinic acetylcholine receptors (nAChRs). Nicotine's reinforcing properties are primarily mediated by activation of the brain's mesolimbic reward circuitry and release of the neurotransmitter dopamine that contribute to the development of addiction. Moreover, nicotine addiction drives repeated intake that results in chronic pulmonary exposure to either tobacco smoke or e-cigarettes despite negative respiratory symptoms. Beyond the brain, nAChRs are also highly expressed in peripheral neurons, epithelia and immune cells, where their activation may cause harmful effects. Thus, nicotine, a key ingredient of both conventional and electronic cigarettes, produces neurological effects that drive addiction and may damage the lungs in the process, producing a complex, multilevel pathological state. We conclude that vaping needs to be studied by multi-disciplinary teams that include pulmonary and neurophysiologists as well as behaviourists and addiction specialists to fully understand their impact on human physiology.
Topics: Brain; Electronic Nicotine Delivery Systems; Humans; Lung; Nicotine; Smoking Cessation
PubMed: 32515030
DOI: 10.1113/JP278388 -
The Western Journal of Emergency... Aug 2019Given the rise in teenage use of electronic nicotine delivery systems ("vaping") in congruence with the increasing numbers of drug-related emergencies, it is critical to... (Review)
Review
Given the rise in teenage use of electronic nicotine delivery systems ("vaping") in congruence with the increasing numbers of drug-related emergencies, it is critical to expand the knowledge of the physical and behavioral risks associated with developmental nicotine exposure. A further understanding of the molecular and neurochemical underpinnings of nicotine's gateway effects allows emergency clinicians to advise patients and families and adjust treatment accordingly, which may minimize the use of tobacco, nicotine, and future substances. Currently, the growing use of tobacco products and electronic cigarettes among teenagers represents a major public health concern. Adolescent exposure to tobacco or nicotine can lead to subsequent abuse of nicotine and other substances, which is known as the gateway hypothesis. Adolescence is a developmentally sensitive time period when risk-taking behaviors, such as sensation seeking and drug experimentation, often begin. These hallmark behaviors of adolescence are largely due to maturational changes in the brain. The developing brain is particularly vulnerable to the harmful effects of drugs of abuse, including tobacco and nicotine products, which activate nicotinic acetylcholine receptors (nAChRs). Disruption of nAChR development with early nicotine use may influence the function and pharmacology of the receptor subunits and alter the release of reward-related neurotransmitters, including acetylcholine, dopamine, GABA, serotonin, and glutamate. In this review, we emphasize that the effects of nicotine are highly dependent on timing of exposure, with a dynamic interaction of nAChRs with dopaminergic, endocannabinoid, and opioidergic systems to enhance general drug reward and reinforcement. We analyzed available literature regarding adolescent substance use and nicotine's impact on the developing brain and behavior using the electronic databases of PubMed and Google Scholar for articles published in English between January 1968 and November 2018. We present a large collection of clinical and preclinical evidence that adolescent nicotine exposure influences long-term molecular, biochemical, and functional changes in the brain that encourage subsequent drug abuse.
Topics: Adolescent; Electronic Nicotine Delivery Systems; Global Health; Humans; Nicotine; Nicotinic Agonists; Substance-Related Disorders
PubMed: 31539325
DOI: 10.5811/westjem.2019.7.41661 -
Cells Apr 2020Cigarette smoke is a known exacerbator of age-related pathologies, such as cardiovascular disease (CVD), atherosclerosis, and cellular aging (senescence). However, the... (Review)
Review
Cigarette smoke is a known exacerbator of age-related pathologies, such as cardiovascular disease (CVD), atherosclerosis, and cellular aging (senescence). However, the role of nicotine and its major metabolite cotinine is yet to be elucidated. Considering the growing amount of nicotine-containing aerosol use in recent years, the role of nicotine is a relevant public health concern. A number of recent studies and health education sites have focused on nicotine aerosol-induced adverse lung function, and neglected cardiovascular (CV) impairments and diseases. A critical review of the present scientific literature leads to the hypothesis that nicotine mediates the effects of cigarette smoke in the CV system by increasing MAPK signaling, inflammation, and oxidative stress through NADPH oxidase 1 (Nox1), to induce vascular smooth muscle cell (VSMC) senescence. The accumulation of senescent VSMCs in the lesion cap is detrimental as it increases the pathogenesis of atherosclerosis by promoting an unstable plaque phenotype. Therefore, nicotine, and most likely its metabolite cotinine, adversely influence atherosclerosis.
Topics: Animals; Atherosclerosis; Cardiovascular System; Cellular Senescence; Disease Models, Animal; Humans; Nicotine; Tobacco Use
PubMed: 32331221
DOI: 10.3390/cells9041035 -
International Journal of Molecular... Sep 2023Nicotine, the primary psychoactive agent in tobacco leaves, has led to the widespread use of tobacco, with over one billion smokers globally. This article provides a... (Review)
Review
Nicotine, the primary psychoactive agent in tobacco leaves, has led to the widespread use of tobacco, with over one billion smokers globally. This article provides a historical overview of tobacco and discusses tobacco dependence, as well as the biological effects induced by nicotine on mammalian cells. Nicotine induces various biological effects, such as neoangiogenesis, cell division, and proliferation, and it affects neural and non-neural cells through specific pathways downstream of nicotinic receptors (nAChRs). Specific effects mediated by α7 nAChRs are highlighted. Nicotine is highly addictive and hazardous. Public health initiatives should prioritize combating smoking and its associated risks. Understanding nicotine's complex biological effects is essential for comprehensive research and informed health policies. While potential links between nicotine and COVID-19 severity warrant further investigation, smoking remains a significant cause of morbidity and mortality globally. Effective public health strategies are vital to promote healthier lifestyles.
Topics: Animals; Humans; Nicotine; Receptors, Nicotinic; Smoking; Tobacco Use Disorder; Mammals
PubMed: 37834017
DOI: 10.3390/ijms241914570 -
Drug and Alcohol Dependence Apr 2018Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported...
BACKGROUND
Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids. The primary objective of this study was to assess the generality of our prior ICSS findings to two additional EC liquids. We also compared effects of "nicotine-free" varieties of these EC liquids on ICSS, as well as binding affinity and/or functional activity of nicotine alone, nicotine-containing EC liquids, and "nicotine-free" EC liquids at nicotinic acetylcholine receptors (nAChRs).
METHODS AND RESULTS
Nicotine alone and nicotine dose-equivalent concentrations of both nicotine-containing EC liquids produced similar lowering of ICSS thresholds at low to moderate nicotine doses, indicating similar reinforcement-enhancing effects. At high nicotine doses, nicotine alone elevated ICSS thresholds (a measure of anhedonia-like behavior) while the EC liquids did not. Nicotine-containing EC liquids did not differ from nicotine alone in terms of binding affinity or functional activity at nAChRs. "Nicotine-free" EC liquids did not affect ICSS, but bound with low affinity at some (e.g., α4ß2) nAChRs.
CONCLUSIONS
These findings suggest that non-nicotine constituents in these EC liquids do not contribute to their reinforcement-enhancing effects. However, they may attenuate nicotine's acute aversive/anhedonic and/or toxic effects, which may moderate the abuse liability and/or toxicity of ECs.
Topics: Animals; Behavior, Animal; Electronic Nicotine Delivery Systems; Male; Models, Animal; Nicotine; Rats; Reinforcement, Psychology; Self Administration; Self Stimulation
PubMed: 29413432
DOI: 10.1016/j.drugalcdep.2017.11.032 -
Expert Opinion on Drug Delivery Dec 2020Unregulated e-cigarette devices and their nicotine content have amplified the potential of e-cigarettes as addictive agents. Several e-cigarette-related parameters have... (Review)
Review
INTRODUCTION
Unregulated e-cigarette devices and their nicotine content have amplified the potential of e-cigarettes as addictive agents. Several e-cigarette-related parameters have been identified altering nicotine's absorption profile, so their potential effects on addiction should be considered. Of these factors, nicotine forms (protonated and free base) play a significant role in the addiction potential yet their impact on nicotine's absorption has been studied with limited research.
AREAS COVERED
Current review aims to emphasize on the possible mechanism behind different absorption profiles of nicotine forms considering their physical states (droplet and vapor phase) and the aerosol particle size, their analysis in e-cigarette research and the regulatory attention warranted by them to combat nicotine addiction in the population due to e-cigarettes.
EXPERT OPINION
The protonated form of nicotine is being correlated with the smooth sensory effects and high nicotine absorption as compared to free base nicotine. With the introduction of nicotine salts, which yield mostly the protonated form, the youth popularity of e-cigarettes has spiked exponentially. While it is important to control nicotine levels in e-cigarette products, attention should also be given to the nicotine forms present in these products in order to address nicotine addiction in the population.
Topics: Adolescent; Aerosols; Electronic Nicotine Delivery Systems; Humans; Nicotine; Particle Size
PubMed: 32842785
DOI: 10.1080/17425247.2020.1814736 -
Cold Spring Harbor Perspectives in... Jun 2021While commendable strides have been made in reducing smoking initiation and improving smoking cessation rates, current available smoking cessation treatment options are... (Review)
Review
While commendable strides have been made in reducing smoking initiation and improving smoking cessation rates, current available smoking cessation treatment options are still only mildly efficacious and show substantial interindividual variability in their therapeutic responses. Therefore, the primary goal of preclinical research has been to further the understanding of the neural substrates and genetic influences involved in nicotine's effects and reassess potential drug targets. Pronounced advances have been made by investing in new translational approaches and placing more emphasis on bridging the gap between human and rodent models of dependence. Functional neuroimaging studies have identified key brain structures involved with nicotine-dependence phenotypes such as craving, impulsivity, withdrawal symptoms, and smoking cessation outcomes. Following up with these findings, rodent-modeling techniques have made it possible to dissect the neural circuits involved in these motivated behaviors and ascertain mechanisms underlying nicotine's interactive effects on brain structure and function. Likewise, translational studies investigating single-nucleotide polymorphisms (SNPs) within the cholinergic, dopaminergic, and opioid systems have found high levels of involvement of these neurotransmitter systems in regulating the reinforcing aspects of nicotine in both humans and mouse models. These findings and coordinated efforts between human and rodent studies pave the way for future work determining gene by drug interactions and tailoring treatment options to each individual smoker.
Topics: Animals; Humans; Models, Animal; Nicotine; Rodentia; Tobacco Use Disorder; Translational Research, Biomedical
PubMed: 32513669
DOI: 10.1101/cshperspect.a039776