Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Altering the Motivational Function of Nicotine through Conditioning Processes

The collection of chapters in this 55th Nebraska Symposium on Motivation Volume clearly highlights that effective strategies for reducing compulsive tobacco use will require a multifaceted approach in which genetic, neurobiological, individual, and cultural factors are considered. It is difficult, if not impossible, to predict where the next important breakthrough will come from (Bevins & Bardo, 2004; Dethier, 1966; Laidler, 1998). Accordingly, further research that extends and challenges current theory and practice at each of these levels of analysis is needed. The continuing focus of our research program, and the topic of the present chapter, is on the role of Pavlovian conditioning processes involving nicotine. Theoretical and empirical approaches to nicotine dependence that include Pavlovian conditioning processes have lead to important advances in our understanding and treatment of chronic tobacco use (e.g., see Rose, Chapter 8 and Tiffany, Warthen, & Goedecker, Chapter 10 in current Volume). These approaches conceptualize the drug as an unconditioned stimulus (US) or reinforcer. That is, the pharmacological effects of the drug (e.g., reward, analgesia, psychomotor stimulation) enter into an association with stimuli that reliably co-occur with these effects (e.g., paraphernalia, situational cues). Later exposure to these conditioned stimuli (CSs) can evoke conditioned responses (CRs) that increase the chances an individual will seek drug. More recently, we have suggested that the interoceptive stimulus effects of nicotine might also serve as a CS for other appetitive non-drug outcomes (i.e., USs) and/or a stimulus that occasions whether other CS-US associations will or will not occur (i.e., an occasion setter or facilitator; see Bevins & Palmatier, 2004). We have further suggested that such an associative learning history could impact the tenacity of nicotine addiction—e.g., shorten the time between experimentation and dependence, increase the difficulty of quitting, make sustaining abstinence more difficult, etc. At the current time these suggestions are speculative. With this in mind, the present chapter will review the research in this area, as well as highlight some of its historical precursors and suggest some possible future directions for research. In doing so, hopefully the reader will gain an appreciation for how this approach might lead to further insight into how Pavlovian conditioning processes can alter the motivational function of nicotine in a manner that contributes to chronic tobacco use

Salivary cotinine concentrations in daily smokers in Barcelona, Spain: a cross-sectional study

Background: Characterizing and comparing the determinant of cotinine concentrations in different populations should facilitate a better understanding of smoking patterns and addiction. This study describes and characterizes determinants of salivary cotinine concentration in a sample of Spanish adult daily smoker men and women. Methods: A cross-sectional study was carried out between March 2004 and December 2005 in a representative sample of 1245 people from the general population of Barcelona, Spain. A standard questionnaire was used to gather information on active tobacco smoking and passive exposure, and a saliva specimen was obtained to determine salivary cotinine concentration. Two hundred and eleven adult smokers (>16 years old) with complete data were included in the analysis. Determinants of cotinine concentrations were assessed using linear regression models. Results: Salivary cotinine concentration was associated with the reported number of cigarettes smoked in the previous 24 hours (R2 = 0.339; p < 0.05). The inclusion of a quadratic component for number of cigarettes smoked in the regression analyses resulted in an improvement of the fit (R2 = 0.386; p < 0.05). Cotinine concentration differed significantly by sex, with men having higher levels. Conclusion: This study shows that salivary cotinine concentration is significantly associated with the number of cigarettes smoked and sex, but not with other smoking-related variables

Is There Any Association between Use of Smokeless Tobacco Products and Coronary Heart Disease in Bangladesh?

BACKGROUND: Most epidemiological studies exploring the association between smokeless tobacco (SLT) use and coronary heart disease (CHD) have been in Western populations, and have focused on SLT products used in those countries. Few studies come from South Asian countries. Our objective was to determine the association between SLT use and CHD among non-smoking adults in Bangladesh. METHODS: A matched case-control study of non-smoking Bangladeshi adults aged 40–75 years was conducted in 2010. Incident cases of CHD were selected from two cardiac hospitals. Community controls, matched to CHD cases, were selected from neighbourhoods, and hospital controls were selected from outpatient departments of the same hospitals. The Rose Angina Questionnaire (RAQ) was also used to re-classify cases and controls. RESULTS: The study enrolled 302 cases, 1,208 community controls and 302 hospital controls. Current use was higher among community controls (38%) compared to cases (33%) and hospital controls (32%). Current use of SLT was not significantly associated with an increased risk of CHD when community controls were used (adjusted OR 0.87, 95% CI 0.63–1.19), or when hospital controls were used (adjusted OR 1.00, 95% CI 0.63–1.60), or when both control groups were combined (adjusted OR 1.00, 95% CI 0.74–1.34). Risk of CHD did not increase with use of individual types except gul, frequency, duration, past use of SLT products, or using the RAQ to re-classify cases and controls. There was a significant association between gul use and CHD when both controls were combined (adjusted OR 2.93, 95% CI 1.28–6.70). CONCLUSIONS: There was no statistically significant association between SLT use in general and CHD among non-smoking adults in Bangladesh. Further research on the association between gul use and CHD in Bangladesh along with SLT use and CHD in other parts of the subcontinent will guide public health policy and interventions that focus on SLT-related diseases.Muhammad Azia Rahman, Nicola Spurrier, Mohammad Afzal Mahmood, Mahmudur Rahman, Soehl Reza Choudhury and Stephen Leede

Examining the effectiveness of general practitioner and nurse promotion of electronic cigarettes versus standard care for smoking reduction and abstinence in hardcore smokers with smoking-related chronic disease:protocol for a randomised controlled trial

BACKGROUND: Despite the clear harm associated with smoking tobacco, many people with smoking-related chronic diseases or serious mental illnesses (SMI) are unwilling or unable to stop smoking. In many cases, these smokers have tried and exhausted all methods to stop smoking and yet clinicians are repeatedly mandated to offer them during routine consultations. Providing nicotine through electronic cigarettes (e-cigarettes) may reduce the adverse health consequences associated with tobacco smoking, but these are not currently offered. The aim of this study is to examine the feasibility, acceptability and effectiveness of general practitioners (GPs) and nurses delivering a brief advice intervention on e-cigarettes and offering an e-cigarette starter pack and patient support resources compared with standard care in smokers with smoking-related chronic diseases or SMI who are unwilling to stop smoking. METHODS/DESIGN: This is an individually randomised, blinded, two-arm trial. Smokers with a smoking-related chronic condition or SMI with no intention of stopping smoking will be recruited through primary care registers. Eligible participants will be randomised to one of two groups if they decline standard care for stopping smoking: a control group who will receive no additional support beyond standard care; or an intervention group who will receive GP or nurse-led brief advice about e-cigarettes, an e-cigarette starter pack with accompanying practical support booklet, and telephone support from experienced vapers and online video tutorials. The primary outcome measures will be smoking reduction, measured through changes in cigarettes per day and 7-day point-prevalence abstinence at 2 months. Secondary outcomes include smoking reduction, 7-day point-prevalence abstinence and prolonged abstinence at 8 months. Other outcomes include patient recruitment and follow-up, patient uptake and use of e-cigarettes, nicotine intake, contamination of randomisation and practitioner adherence to the delivery of the intervention. Qualitative interviews will be conducted in a subsample of practitioners, patients and the vape team to garner their reactions to the programme. DISCUSSION: This is the first randomised controlled trial to investigate whether e-cigarette provision alongside a brief intervention delivered by practitioners leads to reduced smoking and abstinence among smokers with smoking-related chronic diseases or SMI. TRIAL REGISTRATION: ISRCTN registry, ISRCTN59404712. Registered 28/11/17

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Family structure, parent-child conversation time and substance use among Chinese adolescents

<p>Abstract</p> <p>Background</p> <p>The family plays a vital role in shaping adolescent behaviours. The present study investigated the associations between family structure and substance use among Hong Kong Chinese adolescents.</p> <p>Methods</p> <p>A total of 32,961 Form 1 to 5 (grade 7-12 in the US) Hong Kong students participated in the Youth Smoking Survey in 2003-4. An anonymous questionnaire was used to obtain information about family structure, daily duration of parent-child conversation, smoking, alcohol drinking and drug use. Logistic regression was used to calculate the adjusted odds ratios (OR) for each substance use by family structure.</p> <p>Results</p> <p>Adjusting for sex, age, type of housing, parental smoking and school, adolescents from non-intact families were significantly more likely to be current smokers (OR = 1.62), weekly drinkers (OR = 1.72) and ever drug users (OR = 1.72), with significant linear increases in ORs from maternal, paternal to no-parent families compared with intact families. Furthermore, current smoking (OR = 1.41) and weekly drinking (OR = 1.46) were significantly more common among adolescents from paternal than maternal families. After adjusting for parent-child conversation time, the ORs for non-intact families remained significant compared with intact families, but the paternal-maternal differences were no longer significant.</p> <p>Conclusions</p> <p>Non-intact families were associated with substance use among Hong Kong Chinese adolescents. The apparently stronger associations with substance use in paternal than maternal families were probably mediated by the poorer communication with the father.</p