Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.
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http://dx.doi.org/10.1038/nn.4540 | DOI Listing |
Neuropharmacology
January 2025
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Nicotine use remains one of the leading causes of preventable deaths in the United States and, while the prevalence of combustible cigarette use has declined over the past few years, the popularity of electronic nicotine delivery systems continues to rise. Vaping is not without risks, and its long-term effects, particularly in vulnerable populations, remain largely unknown. This study introduces a novel, oronasal-restricted, nicotine vapor self-administration mouse model to investigate the impact of nicotine concentration, genotype, sex, and age on self-administration and behavioral response to nicotine.
View Article and Find Full Text PDFHealth Econ
January 2025
Centro de Investigaciones Económicas y Empresariales, Universidad Privada Boliviana, La Paz, Bolivia.
In this research we show that ambitious increases in tobacco tax rates can substantially reduce tobacco consumption, increase fiscal revenue, and provide net positive social benefits even in contexts of low consumption prevalence and intensity. Low nicotine intake still constitutes a grave disease risk factor, and the effectiveness of tax increases might be questioned if income effects are small. We adapt spatial variation of price methodologies to deal with low prevalence and intensity, censored data, and small samples using the Bolivian case as an illustration.
View Article and Find Full Text PDFNeurobiol Learn Mem
January 2025
School of Psychology, University of New South Wales, Australia. Electronic address:
Humans and animals use information about future access to rewards to influence their behaviour in the present, however the evidence for this is largely anecdotal. Here we use the nicotine intravenous self-administration paradigm to ask whether rats can use an auditory stimulus signalling a long (450 s) signalled time-out on the next trial to influence their nicotine intake in the present. Rats were trained to choose between low (15 µg/kg/infusion), medium (30 µg/kg/infusion) or high (60 µg/kg/infusion) doses of nicotine on any given trial.
View Article and Find Full Text PDFBMC Public Health
January 2025
School of Public Health, Faculty of Health, University of Technology Sydney, Level 8, Building 10, 235-253 Jones St, Ultimo, NSW, Australia.
Background: While some general patterns and trends of health information seeking and literacy in the Australian population are known, there is a need to understand these behaviours and skills specific to the focus areas outlined in the National Preventive Health Strategy (NPHS).
Methods: In response, this study employed a cross-sectional online survey of adults in the Australian general population (n = 1509) to investigate their knowledge and health information seeking behaviour regarding the NPHS' seven focus areas. It also explored primary care practitioners as a preventive health information source.
Free Radic Biol Med
January 2025
VA San Diego Healthcare System, San Diego, CA, USA; Department of Anesthesiology, School of Medicine, University of California San Diego, USA.
Inhaling aerosols from electronic nicotine delivery systems, such as e-cigarettes (e-cigs), may pose health risks beyond those caused by nicotine intake. Exposure to e-cig aerosols can lead to the release of exosomes and metabolites into the bloodstream, potentially affecting mitochondrial physiology across the body, leading to chronic inflammatory diseases. In this study we assessed the effects of e-cig use by young healthy human subjects on the circulating exosome profile and markers of cell stress, and also defined the effects of e-cig user plasma on mitochondrial function in endothelial cells (EA.
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