Ciclo de charlas: Envejecimiento activo y salud de las personas mayores. Cuarto Encuentro. Tabaquismo en las personas mayores ¿Qué debemos saber?

Esta charla, a cargo de la licenciada Silvia Rey, ronda tres grandes temas: Epidemiología del tabaquismo en Personas Mayores en la provincia de Buenos Aires; Rol del equipo de salud en la cesación tabáquica y, por último, Intervenciones de cesación tabáquica en Personas Mayores. Con respecto al primer ítem se desarrollan nociones tales como Envejecimiento saludable y entornos físicos y sociales. Luego se explicitan las medidas propuestas por la OMS que debe tomar el personal de la salud, a saber: detección precoz, tratamiento inmediato de las enfermedades no transmisibles y factores de riesgos modificables. Se parte de considerar al tabaquismo como una enfermedad no transmisible en sí misma, a la vez que factor de riesgo para seis de las ocho enfermedades no transmisibles más frecuentes. Más tarde se pone de relieve la creación de entornos que promuevan la salud. Por último, se tratan los siguientes puntos: Rol del equipo de salud: Intervención positiva e Intervención negativa: características; El consumo de tabaco como problema de Salud Pública a nivel mundial. Descripción del tabaquismo como enfermedad: adictiva, crónica, recidivante. Métodos para dejar de fumar: efectividad. Intervenciones breves e intensivas: características. Los 5 pasos de la Intervención breve. Dejar de fumar como proceso. Tratamiento multicomponente: abordaje farmacológico y cognitivo conductual. Los beneficios de dejar de fumar a cualquier edad.

Prevalence of tobacco dependence and associated factors among patients with schizophrenia attending their treatments at southwest Ethiopia; hospital-based cross-sectional study.

BACKGROUND: Tobacco smoking is the most typically employed in patients with mental disorders; among them, patients with schizophrenia are the very best users. The rate of smoking among patients with schizophrenia is between two and three times greater than the general population in western countries. However, there is a scarcity of studies on the magnitude and associated factors of tobacco dependence among patients with schizophrenia in Ethiopia. Therefore, we assessed the prevalence of tobacco dependence and associated factors among patients with schizophrenia at Mettu Karl referral, Bedelle, and Agaro hospitals, Southwest, Ethiopia. METHOD: Hospital-based the multistage stratified cross-sectional study design was conducted among 524 patients with schizophrenia who are on treatment. Fagerstrom Test for Nicotine Dependence (FTND) was used to screen the prevalence of tobacco dependence. Analysis of data was done using SPSS version 24. RESULT: The prevalence of tobacco dependence among study participants was 22.3% (95% CI) (18.6, 26). Concerning the severity of tobacco dependence, 3.5%, 13.8%, and 5% of the respondents report moderate, high, and very high levels of tobacco dependence respectively. The proportions of tobacco dependence among male schizophrenic patients 88 (25.8%) were higher compared to their counterparts 27 (15.5%). After controlling the effects of cofounders in the final regression analysis, male gender (AOR 2.19, 95% CI = 1.25, 3.83), being on treatment for more than 5years (AOR 4.37, 95% CI = 2.11, 9.02), having a history of admission (AOR 4.01, 95% CI = 1.99, 8.11), and family history of mental illness (AOR 1.90, 95% CI = 1.04, 3.48) were shown to have a significant positive association with tobacco dependence. CONCLUSION AND RECOMMENDATION: A study show a significant proportion of tobacco dependence among people living with schizophrenia. Factors like, being male gender, being on treatment for more than 5 years, having a history of admission, and family history of mental illness was found to have a significant positive association with tobacco dependence. Hence, there is a need for coordinated and comprehensive management clinically to manage tobacco dependence along with identified risk factors in patients with schizophrenia. Also the finding call for the clinicians, managers, ministry of health and other stakeholders on the substance use prevention strategies that target personal and environmental control.

Role of cytokine and neurotrophic factors in nicotine addiction in the conditioned place preference paradigm.

The mechanisms involved in the maintenance of cigarette smoking and nicotine reward remain unclear. Immune response might play an important role in this context. Nicotine may induce both central and systemic inflammatory responses as well as changes in the regulation of brain-derived neurotrophic factor (BDNF). The conditioned place preference (CPP) is a method used for the evaluation of nicotine-induced reward, reproducing nicotine-seeking behavior in humans. So far, there are no studies investigating the relationship between neuroinflammation and nicotine-induced CPP. This study aimed to evaluate the levels of inflammatory mediators and neurotrophic factors in key areas of the central nervous system (CNS) of mice subject to nicotine-induced CPP. CPP was induced with an intraperitoneal administration of 0.5 mg/kg of nicotine in male Swiss mice, using an unbiased protocol. Control group received vehicle by the same route. The levels of cytokines, chemokines, and neurotrophic factors were measured using Enzyme-Linked Immunosorbent Assay (ELISA) in the brain after CPP test. As expected, nicotine induced place preference behavior. In parallel, we observed increased peripheral levels of IL-6 and IL-10 alongside increased hippocampal levels of NGF but decreased GDNF in mice treated with nicotine compared to controls. In the striatum, nicotine promoted decrease of IL-1ß, IL-10 and GDNF levels, while the levels of all the mediators were similar between groups in the pre-frontal cortex. Our results provide evidence on the role of cytokines and neurotrophic factors in nicotine-induced CPP in mice.

More than just statics: Temporal dynamic changes of intrinsic brain activity in cigarette smoking.

Smoking is companied with altered intrinsic activity of the brain measured by amplitude of low-frequency fluctuation. Evidence has revealed that human brain activity is a highly dynamic and rapidly changing system. How exactly cigarette smoking affect temporal dynamic intrinsic brain activity is not fully understood nor is it clear how smoking severity influences spontaneous brain activity. Dynamic amplitude of low-frequency fluctuation (dALFF) was used to examine the dynamic temporal variability in 93 participants (63 smokers, 30 nonsmokers). We further divided smokers into light and heavy smokers. The temporal variability in intrinsic brain activity among these groups was compared. Correlation analyses were performed between dALFF in areas showing group differences and smoking behaviour (e.g., the Fagerström Test for Nicotine Dependence [FTND] scores and pack-years). Smokers showed significantly increased dALFF in the left inferior/middle frontal gyrus, right orbitofrontal gyrus, right insula, left superior/medial frontal gyrus and right middle frontal gyrus than nonsmokers. Light smokers showed increased dALFF variability in the left prefrontal cortex. Heavy smokers showed increased dynamics in specific brain regions, including the right postcentral gyrus, right insula and left precentral gyrus. Furthermore, the temporal variability in dALFF in the left superior/medial frontal gyrus, left superior/middle frontal gyrus, right middle frontal gyrus and right insula was positively correlated with pack-years or FTND. Combined, these results suggest that smokers increase stable and persistent spontaneous brain activity in prefrontal cortex, involved impaired gold-directed action and value-based decision-making. In addition, individuals with heavier smoking severity show increased perturbance on spontaneous brain activity of perception and sensorimotor, related to increased reliance.

Evaluation of Micronuclei and Cytomorphometric Changes in Patients with Different Tobacco Related Habits Using Exfoliated Buccal Cells.

BACKGROUND: Tobacco is one of the main reasons behind the occurrence of oral cancer. Oral cancer, even though being the tenth most common cancer in the world, gets diagnosed at an advanced stage and ends up with poor prognosis. So early diagnosis is the need of the hour. Our study aimed to evaluate the genotoxic changes in patients with different tobacco habits using buccal exfoliated cells. METHODS: Buccal smears were taken from smokers (30), smokeless tobacco users (30), combined tobacco users (30) and controls (30) with clinically normal oral mucosa. All the smears were stained with Papanicolaou stain and Feulgen stain and viewed under light microscope for the evaluation of mean number of micronuclei, mean micronuclei per cell, frequency of cells showing micronuclei, nuclear area, cytoplasmic area, nuclear-cytoplasmic ratio. RESULTS: Mean number of micronuclei, mean micronuclei per cell, frequency of cells showing micronuclei, and nuclear area were significantly increased in tobacco users than controls, especially in combined tobacco users. Nuclear-cytoplasmic ratio was increased and cytoplasmic area was decreased in tobacco users than controls. CONCLUSION: Tobacco in any consumable form is genotoxic. Smoking and smokeless tobacco, when consumed together, synergistically causes higher genetic damage. Different tobacco habits have different deleterious effects on oral mucosa, and these effects are more pronounced when the patients have combined habits. So, detecting the genotoxic changes through exfoliative cytology can be used as a simple yet reliable marker for early detection of carcinogenesis.
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Nicotine addiction: Translational insights from circuit neuroscience.

Contemporary neuroscience aims to understand how neuronal activity produces internal processes and observable behavioral states. This aim crucially depends on systems-level, circuit-based analyses of the working brain, as behavioral states arise from information flow and connectivity within and between discrete and overlapping brain regions, forming circuits and networks. Functional magnetic resonance imaging (fMRI), offers a key to advance circuit neuroscience; fMRI measures inter and intra- regional circuits at behaviorally relevant spatial-temporal resolution. Herein, we argue that cross-sectional observations in human populations can be best understood via mechanistic and causal insights derived from brain circuitry obtained from preclinical fMRI models. Using nicotine addiction as an exemplar of a circuit-based substance use disorder, we review fMRI-based observations of a circuit that was first shown to be disrupted among human smokers and was recently replicated in rodent models of nicotine dependence. Next, we discuss circuits that predispose to nicotine dependence severity and their interaction with circuits that change as a result of chronic nicotine administration using a rodent model of dependence. Data from both clinical and preclinical fMRI experiments argue for the utility of fMRI studies in translation and reverse translation of a circuit-based understanding of brain disease states. We conclude by discussing the future of circuit neuroscience and functional neuroimaging as an essential bridge between animal models and human populations to the understanding of brain function in health and disease.

Adolescent nicotine induces depressive and anxiogenic effects through ERK 1-2 and Akt-GSK-3 pathways and neuronal dysregulation in the nucleus accumbens.

Long-term tobacco dependence typically develops during adolescence and neurodevelopmental nicotine exposure is associated with affective disturbances that manifest as a variety of neuropsychiatric comorbidities in clinical and preclinical studies, including mood and anxiety-related disorders. The nucleus accumbens shell (NASh) is critically involved in regulating emotional processing, and both molecular and neuronal disturbances in this structure are associated with mood and anxiety-related pathologies. In the present study, we used a rodent model of adolescent neurodevelopmental nicotine exposure to examine the expression of several molecular biomarkers associated with mood/anxiety-related phenotypes. We report that nicotine exposure during adolescence (but not adulthood) induces profound upregulation of the ERK 1-2 and Akt-GSK-3 signalling pathways directly within the NASh, as well as downregulation of local D1R expression that persists into adulthood. These adaptations were accompanied by decreases in τ, α, ß, and γ-band oscillatory states, hyperactive medium spiny neuron activity with depressed bursting rates, and anxiety and depressive-like behavioural abnormalities. Pharmacologically targeting these molecular and neuronal adaptations revealed that selective inhibition of local ERK 1-2 and Akt-GSK-3 signalling cascades rescued nicotine-induced high-γ-band oscillatory signatures and phasic bursting rates in the NASh, suggesting that they are involved in mediating adolescent nicotine-induced depressive and anxiety-like neuropathological trajectories.

Gene-based association analysis reveals involvement of LAMA5 and cell adhesion pathways in nicotine dependence in African- and European-American samples.

Nicotine dependence (ND) is a chronic brain disorder that causes heavy social and economic burdens. Although many susceptibility genetic loci have been reported, they can explain only approximately 5%-10% of the genetic variance for the disease. To further explore the genetic etiology of ND, we genotyped 242 764 SNPs using an exome chip from both European-American (N = 1572) and African-American (N = 3371) samples. Gene-based association analysis revealed 29 genes associated significantly with ND. Of the genes in the AA sample, six (i.e., PKD1L2, LAMA5, MUC16, MROH5, ATP8B1, and FREM1) were replicated in the EA sample with p values ranging from 0.0031 to 0.0346. Subsequently, gene enrichment analysis revealed that cell adhesion-related pathways were significantly associated with ND in both the AA and EA samples. Considering that LAMA5 is the most significant gene in cell adhesion-related pathways, we did in vitro functional analysis of this gene, which showed that nicotine significantly suppressed its mRNA expression in HEK293T cells (p < 0.001). Further, our cell migration experiment showed that the migration rate was significantly different in wild-type and LAMA5-knockout (LAMA5-KO)-HEK293T cells. Importantly, nicotine-induced cell migration was abolished in LAMA5-KO cells. Taken together, these findings indicate that LAMA5, as well as cell adhesion-related pathways, play an important role in the etiology of smoking addiction, which warrants further investigation.

Increased striatal functional connectivity is associated with improved smoking cessation outcomes: A preliminary study.

The striatum is the critical area of reward processing and has been repeatedly linked to nicotine addiction. However, it remains unclear whether different smoking cessation outcomes (relapse or not) are associated with different functional connectivity changes of the striatum during smoking cessation treatment. A total of 30 treatment-seeking smokers were recruited in the study and underwent magnetic resonance imaging (MRI) scans immediately before and after a 12-week treatment with varenicline. After the 12-week treatment with varenicline, 14 subjects relapsed to smoking (relapsers), whereas 16 not relapsed (nonrelapsers). Changes in resting-state functional connectivity (rsFC) across groups and visits were assessed using repeated measures analysis of covariance (ANCOVA). Significant interaction effects were detected: (1) between left nucleus accumbens (NAc) and left orbitofrontal cortex (OFC), insula, inferior frontal gyrus (IFG), and bilateral precuneus; (2) between right NAc and left insula, IFG, and bilateral dorsolateral prefrontal cortex (DLPFC); and (3) between bilateral putamen and left precuneus. Post hoc region-of-interest analyses in brain areas showing interaction effects indicated significantly decreased rsFC after treatment compared with before treatment in relapsers but opposite longitudinal changes in nonrelapers. These novel findings suggest that increased striatal rsFC is associated with improved smoking cessation outcomes. These striatal functional circuits may serve as potential therapeutic targets for more efficacious treatment of nicotine addiction.

Estimating the Population Health Impact of Recently Introduced Modified Risk Tobacco Products: A Comparison of Different Approaches.

INTRODUCTION: Various approaches have been used to estimate the population health impact of introducing a Modified Risk Tobacco Product (MRTP). AIMS AND METHODS: We aimed to compare and contrast aspects of models considering effects on mortality that were known to experts attending a meeting on models in 2018. RESULTS: Thirteen models are described, some focussing on e-cigarettes, others more general. Most models are cohort-based, comparing results with or without MRTP introduction. They typically start with a population with known smoking habits and then use transition probabilities either to update smoking habits in the "null scenario" or joint smoking and MRTP habits in an "alternative scenario". The models vary in the tobacco groups and transition probabilities considered. Based on aspects of the tobacco history developed, the models compare mortality risks, and sometimes life-years lost and health costs, between scenarios. Estimating effects on population health depends on frequency of use of the MRTP and smoking, and the extent to which the products expose users to harmful constituents. Strengths and weaknesses of the approaches are summarized. CONCLUSIONS: Despite methodological differences, most modellers have assumed the increase in risk of mortality from MRTP use, relative to that from cigarette smoking, to be very low and have concluded that MRTP introduction is likely to have a beneficial impact. Further model development, supplemented by preliminary results from well-designed epidemiological studies, should enable more precise prediction of the anticipated effects of MRTP introduction. IMPLICATIONS: There is a need to estimate the population health impact of introducing modified risk nicotine-containing products for smokers unwilling or unable to quit. This paper reviews a variety of modeling methodologies proposed to do this, and discusses the implications of the different approaches. It should assist modelers in refining and improving their models, and help toward providing authorities with more reliable estimates.

Tobacco use disorder and the lungs.

This narrative review provides a summary of the impact of tobacco smoking on the respiratory system and the benefits of smoking cessation. Tobacco smoking is one of the leading preventable causes of death world-wide and a major risk factor for lung cancer and chronic obstructive pulmonary disease. Smoking is also associated with an increased risk of respiratory infections and appears to be related to poorer outcomes among those with COVID-19. Non-smokers with second-hand smoke exposure also experience significant adverse respiratory effects. Smoking imposes enormous health- and non-health-related costs to societies. The benefits of smoking cessation, in both prevention and management of respiratory disease, have been known for decades and, to this day, cessation support remains one of the most important cost-effective interventions that health professionals can provide to people who smoke. Cessation at any age confers substantial health benefits, even in smokers with established morbidities. As other treatments for chronic respiratory disease advance and survival rates increase, smoking cessation treatment will become even more relevant. While smoking cessation interventions are available, the offer of these by clinicians and uptake by patients remain limited.

The Impact of Electronic Nicotine Delivery System (ENDS) Flavors on Nicotinic Acetylcholine Receptors and Nicotine Addiction-Related Behaviors.

Over the past two decades, combustible cigarette smoking has slowly declined by nearly 11% in America; however, the use of electronic cigarettes has increased tremendously, including among adolescents. While nicotine is the main addictive component of tobacco products and a primary concern in electronic cigarettes, this is not the only constituent of concern. There is a growing market of flavored products and a growing use of zero-nicotine e-liquids among electronic cigarette users. Accordingly, there are few studies that examine the impact of flavors on health and behavior. Menthol has been studied most extensively due to its lone exception in combustible cigarettes. Thus, there is a broad understanding of the neurobiological effects that menthol plus nicotine has on the brain including enhancing nicotine reward, altering nicotinic acetylcholine receptor number and function, and altering midbrain neuron excitability. Although flavors other than menthol were banned from combustible cigarettes, over 15,000 flavorants are available for use in electronic cigarettes. This review seeks to summarize the current knowledge on nicotine addiction and the various brain regions and nicotinic acetylcholine receptor subtypes involved, as well as describe the most recent findings regarding menthol and green apple flavorants, and their roles in nicotine addiction and vaping-related behaviors.

Evaluating the Changes of White Matter Microstructures in Tobacco Addicts Based on Diffusion Tensor Imaging.

BACKGROUND The tract-based spatial statistics (TBSS) method was used to investigate the changes of white matter microstructure in tobacco addicts, and to analyze its correlation with smoking index, smoking years, and daily smoking amount. MATERIAL AND METHODS Routine magnetic resonance imaging (excluding intracranial lesions) and diffusion tensor imaging (DTI) sequence scanning were performed in 156 nicotine addicts (nicotine dependence group) and 81 non-nicotine addicts (control group) recruited from the study group. TBSS method was used to preprocess DTI data, and age and education level were taken as covariables to statistically analyze relevant parameters between nicotine dependence group and control group, such as fractional anisotropy (FA) value and smoking index. Spearman correlation analysis was performed on smoking status and FA values in brain regions with significant differences between nicotine dependent group and control group, and the test level alpha was 0.05. RESULTS Compared with control group, FA values of white matter in part of the posterior limb of the right inner capsule (r=-0.428, P=0.003), the right superior radiating crown (r=-0.136, P=0.004), the right posterior radiating crown (r=-0.229, P=0.003), the right superior longitudinal bundle (r=-0.474, P=0.002), the right inferior longitudinal bundle (r=-0.354, P=0.003) and the inferior frontal occipital bundle (r=-0.310, P=0.002) were decreased, which were negatively correlated with smoking index (P<0.05). CONCLUSIONS Nicotine can damage the microstructure of white matter in specific brain regions and damage neurons, with cumulative effects.

Prevalence of substance use disorders in Punjab: Findings from National Mental Health Survey.

Background & objectives: Substance use disorders are a major public health concern in Punjab. However, reliable estimates of prevalence of substance use disorders are not available for the State. The present study reports estimates of prevalence of substance use disorders in Punjab, conducted as part of National Mental Health Survey, India. Methods: Using multistage stratified random cluster sampling, 2895 individuals from 719 households of 60 clusters (from 4 districts of Punjab) were interviewed. Mini International Neuropsychiatric Interview and Fagerstrom nicotine dependence scale were used to assess substance use disorders. Results: The sample comprised almost equal numbers of males and females. Nearly 80 per cent had less than or equal to high school education, and 70 per cent were married. The weighted prevalence of alcohol and other substance use disorders was 7.9 and 2.48 per cent, respectively. The prevalence of tobacco dependence was 5.5 per cent; 35 per cent households had one person with substance use disorder. The prevalence was highest in the productive age group (30-39 yr), urban metro and less educated persons. The prevalence of alcohol and other substance use disorders was much higher in Punjab as compared to other States where survey was done. Tobacco dependence was lowest in Punjab. Majority (87%) of the persons with substance use disorders did not suffer from any other mental disorder. Treatment gap was 80 per cent. Interpretation & conclusions: Punjab has a high burden of substance use disorders. The estimates will help clinicians and policymakers to plan the strategies against the menace of substance use disorders effectively.

Intranasal mesenchymal stem cell secretome administration markedly inhibits alcohol and nicotine self-administration and blocks relapse-intake: mechanism and translational options.

BACKGROUND: Chronic consumption of most drugs of abuse leads to brain oxidative stress and neuroinflammation, which inhibit the glutamate transporter GLT-1, proposed to perpetuate drug intake. The present study aimed at inhibiting chronic ethanol and nicotine self-administration and relapse by the non-invasive intranasal administration of antioxidant and anti-inflammatory secretome generated by adipose tissue-derived activated mesenchymal stem cells. The anti-addiction mechanism of stem cell secretome is also addressed. METHODS: Rats bred for their alcohol preference ingested alcohol chronically or were trained to self-administer nicotine. Secretome of human adipose tissue-derived activated mesenchymal stem cells was administered intranasally to animals, both (i) chronically consuming alcohol or nicotine and (ii) during a protracted deprivation before a drug re-access leading to relapse intake. RESULTS: The intranasal administration of secretome derived from activated mesenchymal stem cells inhibited chronic self-administration of ethanol or nicotine by 85% and 75%, respectively. Secretome administration further inhibited by 85-90% the relapse "binge" intake that occurs after a protracted drug deprivation followed by a 60-min drug re-access. Secretome administration fully abolished the oxidative stress induced by chronic ethanol or nicotine self-administration, shown by the normalization of the hippocampal oxidized/reduced glutathione ratio, and the neuroinflammation determined by astrocyte and microglial immunofluorescence. Knockdown of the glutamate transporter GLT-1 by the intracerebral administration of an antisense oligonucleotide fully abolished the inhibitory effect of the secretome on ethanol and nicotine intake. CONCLUSIONS: The non-invasive intranasal administration of secretome generated by human adipose tissue-derived activated mesenchymal stem cells markedly inhibits alcohol and nicotine self-administration, an effect mediated by the glutamate GLT-1 transporter. Translational implications are envisioned.

Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms.

BACKGROUND: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown. METHODS: Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age. RESULTS: Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968. CONCLUSIONS: These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.

Exercise during abstinence normalizes ultrastructural synaptic plasticity associated with nicotine-seeking following extended access self-administration.

Nicotine-craving progressively increases, or incubates, over abstinence following extended access self-administration. While not yet examined for nicotine, the incubation of cocaine-seeking is accompanied by changes in synaptic plasticity in the nucleus accumbens. Here, we determined whether such changes also accompany enhanced nicotine-seeking following extended access self-administration and abstinence, and whether exercise, a potential intervention for nicotine addiction, may exert its efficacy by normalizing these changes. Given that in humans, tobacco/nicotine use begins during adolescence, we used an adolescent-onset model. Nicotine-seeking was assessed in male rats following extended access nicotine or saline self-administration (23-hr/day, 10 days) and 10 days of abstinence, conditions known to induce the incubation of nicotine-seeking, using a within-session extinction/cue-induced reinstatement procedure. A subset of rats had 2-hr/day access to a running wheel during abstinence. Ultrastructural alterations of synapses in the nucleus accumbens core and shell were examined using electron microscopy. Nicotine-seeking was elevated following extended access self-administration and abstinence (in sedentary group), and levels of seeking were associated with an increase in the density of asymmetric (excitatory) and symmetric (inhibitory) synapses onto dendrites in the core, as well as longer asymmetric synapses onto spines, a marker of synaptic potentiation, in both the core and shell. Exercise normalized each of these changes; however, in the shell, exercise and nicotine similarly increased the synapse length. Together, these findings indicate an association between nicotine-seeking and synaptic plasticity in the nucleus accumbens, particularly the core, and indicate that the efficacy of exercise to reduce nicotine-seeking may be mediated by reversing these adaptations.