58 resultados para Nicotine
em Deakin Research Online - Australia
Resumo:
It has been reported previously that leptin may be involved in nicotine's ability to reduce body weight. Our aim was to investigate whether the anorexic action of nicotine is related to the actions of leptin by utilizing lean leptin-sensitive and obese leptin-resistant Psammomys obesus. Lean and obese P. obesus were assigned to receive nicotine sulphate at 6, 9 or 12 mg/day or saline (control) for 9 days (n = 6-10 in each group), administered using mini-osmotic pumps. Food intake, body weight, plasma leptin concentrations, plasma insulin and blood glucose were measured at baseline and throughout the study period. Nicotine treatment reduced food intake by up to 40% in lean and obese P. obesus. Plasma leptin levels fell significantly only in lean nicotine-treated animals, whereas no changes were observed in obese nicotine-treated animals. However, both lean and obese nicotine-treated animals had similar reductions in body weight. Our results show that nicotine has dramatic effects on food intake and body weight, however, these changes appear to be independent of the leptin signalling pathway.
Resumo:
Introduction: Neurotic psychopathology has been extensively examined as a risk factor for nicotine dependence (ND). Genetic stratification may partially explain variability in risk estimates. Genetic variants that compromise dopaminergic neurotransmission may motivate exposure to dopamine-stimulating agents, including nicotine. The 7-repeat allele of a Variable Number Tandem Repeat (VNTR) polymorphism in DRD4 (and evolutionary derivatives 5, 6, and 8 repeats; 7R+) is associated with reduced dopamine receptor function. The purpose of this study was to examine association between both smoking initiation (SI) and progression to ND by young adulthood and (a) history of neuroticism during adolescence, (b) DRD4 7R+, and (c) interaction between neuroticism and DRD4 7R+.
Methods: Participants were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well-being of young Australians across 8 waves (14–24 years). Neuroticism was measured at Waves 3 and 6 (mean 15.9 and 17.4 years). SI was defined as any smoking at any wave. ND was measured at Wave 8 (mean 24.1 years). Genotype data for the DRD4 VNTR were available for 839 participants.
Results: While adolescent neuroticism was associated with SI, evidence for association with progression to ND was weak. However, there was evidence of interaction between neuroticism and DRD4 7R+: The odds of progression to ND among those with a history of neuroticism were more than 3.5-fold higher among 7R+ carriers.
Conclusions: Without considering stratification by 7R+, the association between progression to ND and neuroticism would have been assumed barely significant. However, among those carrying DRD4 7R+, risk of progression was considerably intensified.
Resumo:
Aims To examine the association of adolescent depression and anxiety symptoms with daily smoking and nicotine dependence in young adulthood.
Design A prospective cohort study of adolescent and young adult health (n = 1943). Teen assessments occurred at 6-monthly intervals, with two follow-up assessments in young adulthood (wave 7, 1998; wave 8, 2001–03).
Setting Victoria, Australia.
Participants Students who participated at least once during the first six (adolescent) waves of the cohort study.
Measurements Adolescent depression and anxiety symptomswere assessed using the Revised Clinical Interview Schedule (CIS-R).Young adult tobacco usewas defined as: daily use (6 or 7 days perweek) and dependent use (>4 on the Fagerstrom Test for Nicotine Dependence).
Findings Among adolescent ‘less than daily’ smokers, those with high levels of depression and anxiety symptoms had an increased risk of reporting nicotine dependence in young adulthood [odds ratio (OR) 3.3, 95% confidence interval (CI) 1.2–9.1] compared to young adults who had low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Similarly, in the adjusted model (OR 1.9, 95% CI 1.0–3.4), among adolescent ‘daily’ smokers, those with high levels of depression and anxiety symptoms had an almost two-fold increase in the odds of reporting nicotine dependence in young adulthood compared to young adults with low levels of adolescent depression and anxiety symptoms.
Conclusions Adolescent smokerswith depression and anxiety symptoms are at increased risk for nicotine dependence into young adulthood. They warrant vigilance from primary care providers in relation to tobacco use well into adulthood.
Resumo:
Dopamine is a key neurotransmitter of the mesolimbic reward pathway in the human brain, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. Consequently, the gene encoding TH is a strong candidate for involvement in the genetic component of addiction. The importance of this gene in nicotine dependence is supported by many studies showing a link between nicotine administration and TH expression. A functional tetranucleotide repeat polymorphism within intron 1 of the TH gene (HUMTH01-VNTR) has been shown to modify tobacco use in two independent Caucasian samples from the USA and Australia. Using information drawn from an eight-wave Australian population-based longitudinal study of adolescent health, we tested the effect of the HUMTH01-VNTR on nicotine dependence. Comparisons were made between dependent smokers and non-dependent smokers. These data provide further support for a protective association between the K4 allele and dependent smoking (odds ratio 0.54, 95% confidence interval 0.28-1.0). No associations were observed at any of three other common TH polymorphisms (rs6356, rs6357 and HUMTH01-PstI). Including these data, three independent studies, two of which use identical phenotypes, have now identified a protective relationship between the K4 allele of the functional HUMTH01-VNTR polymorphism and high-level smoking.
Resumo:
Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective), the population assessed (random sample versus clinical population) and diagnostic instrument utilized.
Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD)) for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders.
Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder), although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified.
Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as increasing the risk of panic disorder and generalized anxiety disorder. The literature assessing anxiety disorders increasing smoking and nicotine dependence is inconsistent. Potential issues with the current literature are discussed and directions for future research are suggested.
Resumo:
Delivery of nicotine in the most desirable form is critical in maintaining people's use of tobacco products. Interpretation of results by tobacco industry scientists, studies that measure free-base nicotine directly in tobacco smoke, and the variability of free-base nicotine in smokeless tobacco products all indicate that the form of nicotine delivered to the tobacco user, in addition to the total amount, is an important factor in whether people continue to use the product following their initial exposure. The physiological impact of nicotine varies with the fraction that is in the free-base form and this leads to continued exposure to other toxic tobacco contents and emissions. In addition to evaluating the total nicotine delivered to the user, measuring the fraction of nicotine in the free-base form is critical in understanding and controlling the influence of nicotine on tobacco use.
Resumo:
Nicotine dependence is common in people with mood disorders; however the operative pathways are not well understood. This paper reviews the contribution of inflammation and oxidative stress pathways to the co-association of depressive disorder and nicotine dependence, including increased levels of pro-inflammatory cytokines, increased acute phase proteins, decreased levels of antioxidants and increased oxidative stress. These could be some of the potential pathophysiological mechanisms involved in neuroprogression. The shared inflammatory and oxidative stress pathways by which smoking may increase the risk for development of depressive disorders are in part mediated by increased levels of pro-inflammatory cytokines, diverse neurotransmitter systems, activation the hypothalamic-pituitary-adrenal (HPA) axis, microglial activation, increased production of oxidative stress and decreased levels of antioxidants. Depressive disorder and nicotine dependence are additionally linked imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway that contribute to neuroprogression. These pathways provide a mechanistic framework for understanding the interaction between nicotine dependence and depressive disorder.
Resumo:
In a double-blind placebo-controlled study, we examined the effect of nicotine, a cholinergic agonist, on performance of a prospective memory (ProM) task in young adult volunteers.
Volunteers were required to complete an ongoing lexical decision task while maintaining the ProM task (responding with a different button press to items containing particular target letters). Half of the volunteers were smokers, half were nonsmokers. Half of each group received a single dose (1 mg) of nicotine nasal spray before completing the task; the remaining volunteers received a matched inactive placebo spray.
Nicotine improved performance on the ProM task when volunteers were able to devote resources to that task. Under a variant procedure, where volunteers completed a concurrent auditory monitoring task, ProM performance was impaired under nicotine. Results are discussed in terms of the resource model of ProM, and the arousal model of drug effects.
The data suggest that ProM under the conditions tested here is a resource-needy process, and that nicotine can improve performance by increasing available resources. Increased working memory demands that encourage redirection of resources may impair ProM performance, but the conditions under which these deficits emerge depend upon the subjective allocation of resources across tasks, rather than resource availability per se.
Resumo:
Rationale
Objective
We present two studies that explore the source of nicotine’s enhancement of PM. Experiment 1 tests for effects of nicotine on preparatory attention (PA) for PM target detection. Experiment 2 asks whether nicotine enhances processing of the perceptual attributes of the PM targets.
Materials and methods
Young adult non-smokers matched on baseline performance measures received either 1 mg nicotine or matched placebo via nasal spray. Volunteers completed novel PM tasks at 15 min post-administration.
Results
Experiment 1 confirmed that pre-administration of nicotine to non-smokers improved detection rate for prospective memory targets presented during an attention demanding ongoing task. There was no relationship between PM performance and measures of preparatory attention. In experiment 2, salient targets were more likely to be detected than non-salient targets, but nicotine did not confer any additional advantage to salient targets.
Conclusion
The present study suggests that nicotinic stimulation does not work to enhance perceptual salience of target stimuli (experiment 2), nor does it work through better deployment of preparatory working attention (experiment 1). An alternative explanation that nicotine promotes PM detection by facilitating disengagement from the ongoing task is suggested as a future line of investigation.
Resumo:
Rationale
The present paper asked first whether the cholinergic agonist nicotine improves memory for delayed intentions (prospective memory, ProM) and second whether pharmacological dissociation would support the psychological distinction that is made between strategic (effortful) and automatic (non-effortful) intention activation in prospective memory.
Objectives
To use nicotine as a pharmacological tool with which to examine the neurochemical bases of prospective memory and to dissociate strategic from automatic components of ProM retrieval.
Methods
In three experiments, minimally deprived (2 h) smokers either smoked or abstained prior to completing a standard prospective memory study. This involved participants in the simultaneous processing of a ProM task and a cover task (ongoing between the setting and the recall of the intention). Here, the ongoing task involved lexical decision (LDT), while the ProM task required a response to pre-specified target items occurring within the LDT stimuli. Variations in task instructions were used to manipulate the processing requirements of the ProM task, the attention allocated to the ProM task and the balance of importance assigned to the ongoing and ProM tasks.
Results
In experiment 1, where the ProM processing was automatic, nicotine did not improve ProM accuracy. In experiment 2, where the ProM task involved strategic processing, positive effects of nicotine were observed. In experiment 3, we covaried ProM task instructions, assigned task importance and nicotine conditions. We observed a main effect of nicotine on ProM accuracy, a main effect of task on ProM accuracy and a main effect of assigned task importance on ProM accuracy. There were no interactions between the factors.
Conclusions
Employing both direct and indirect manipulations of strategic engagement, we demonstrated nicotine-induced enhancement of performance on the ProM task. The results are consistent with the view that relatively small changes in instruction and in task variables engage strategic processing in a ProM task and that when these conditions stretch cognitive resources, nicotine may significantly improve performance.
Resumo:
Transcription factors of the plant-specific apetala2/ethylene response factor (AP2/ERF) family control plant secondary metabolism, often as part of signalling cascades induced by jasmonate (JA) or other elicitors. Here, we functionally characterized the JA-inducible tobacco (Nicotiana tabacum) AP2/ERF factor ORC1, one of the members of the NIC2-locus ERFs that control nicotine biosynthesis and a close homologue of ORCA3, a transcriptional activator of alkaloid biosynthesis in Catharanthus roseus. ORC1 positively regulated the transcription of several structural genes coding for the enzymes involved in nicotine biosynthesis. Accordingly, overexpression of ORC1 was sufficient to stimulate alkaloid biosynthesis in tobacco plants and tree tobacco (Nicotiana glauca) root cultures. In contrast to ORCA3 in C. roseus, which needs only the GCC motif in the promoters of the alkaloid synthesis genes to induce their expression, ORC1 required the presence of both GCC-motif and G-box elements in the promoters of the tobacco nicotine biosynthesis genes for maximum transactivation. Correspondingly, combined application with the JA-inducible Nicotiana basic helix–loop–helix (bHLH) factors that bind the G-box element in these promoters enhanced ORC1 action. Conversely, overaccumulation of JAZ repressor proteins that block bHLH activity reduced ORC1 functionality. Finally, the activity of both ORC1 and bHLH proteins was post-translationally upregulated by a JA-modulated phosphorylation cascade, in which a specific mitogen-activated protein kinase kinase, JA-factor stimulating MAPKK1 (JAM1), was identified. This study highlights the complexity of the molecular machinery involved in the regulation of tobacco alkaloid biosynthesis and provides mechanistic insights about its transcriptional regulators.
