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Cardiorespiratory and autonomic impacts of coolants in e-cigarette aerosols
PROJECT SUMMARY / ABSTRACT Coolants such as menthol, WS-3, and WS-23 are widely used in electronic cigarettes (e-cigs) to reduce irritation and enhance appeal—especially among youth. Despite their prevalence, the cardiopulmonary toxicity of these agents remains poorly characterized. Recent work shows that e-cig aerosols can disrupt autonomic nervous system regulation and cardiac electrophysiology, increasing catecholamine release, enhancing sympathetic regulation of cardiac rhythm, and provoking arrhythmias. Proof is also mounting that nicotine’s sympathomimetic traits mediate these pathogenic effects. Preliminary data from our laboratory show that coolants increase systemic nicotine levels, blunt respiratory reflexes, and potentiate arrhythmias upon exposures to e-cigarette aerosols, suggesting a paradoxical role for coolants in suppressing ventilatory responses while intensifying cardiovascular risk. These findings take on added significance in light of recent case reports of sudden cardiac arrest in young e-cigarette users, including some in otherwise healthy individuals. This project will elucidate how e-cigarette coolants alter exposure to harmful and potentially harmful constituents (HPHCs)—particularly nicotine and aldehydes—concurrent with their effects on cardiovascular and respiratory physiology. Using robust murine models with continuous ECG, blood pressure, and pleural pressure telemetry, we will assess how coolants alter the acute and chronic effects of e-cigarette aerosols on cardiac electrophysiology, autonomic tone, ventilatory function, hemodynamics, and toxicant exposure. We will also evaluate how coolant concentration and device power modulate these effects. In parallel, we will determine whether adolescent mice exhibit heightened susceptibility to these effects compared to adults, with attention to sex differences and the persistence of cardiotoxicity after exposure cessation. This comprehensive, multi-modal approach incorporates novel protocols for arrhythmia inducibility, high-resolution physiologic monitoring, and complementary analyses of biomarkers of exposure and effect. By clarifying how coolants interact with HPHCs—especially nicotine and aldehydes—to drive cardiopulmonary injury across age and sex, this work addresses high-priority research areas identified in RFA-OD-25-001, including the toxicological evaluation of e-cigarette constituents and their cardiopulmonary effects. The results will inform regulatory policy and public health strategies aimed at mitigating cardiovascular risk associated with e-cigarette use, particularly among vulnerable youth.
Inter-individual variability in reward seeking and decision making: role of social life and consequence for vulnerability to nicotine
Inter-individual variability refers to differences in the expression of behaviors between members of a population. For instance, some individuals take greater risks, are more attracted to immediate gains or are more susceptible to drugs of abuse than others. To probe the neural bases of inter-individual variability we study reward seeking and decision-making in mice, and dissect the specific role of dopamine in the modulation of these behaviors. Using a spatial version of the multi-armed bandit task, in which mice are faced with consecutive binary choices, we could link modifications of midbrain dopamine cell dynamics with modulation of exploratory behaviors, a major component of individual characteristics in mice. By analyzing mouse behaviors in semi-naturalistic environments, we then explored the role of social relationships in the shaping of dopamine activity and associated beahviors. I will present recent data from the laboratory suggesting that changes in the activity of dopaminergic networks link social influences with variations in the expression of non-social behaviors: by acting on the dopamine system, the social context may indeed affect the capacity of individuals to make decisions, as well as their vulnerability to drugs of abuse, in particular nicotine.
Neuroimmune and Glutamatergic Mechanisms of Nicotine Addiction
Adolescent nicotine exposure disrupts its anxiogenic properties in adulthood
Age-specific memory impairment induced by co-exposure to nicotine and a synthetic cannabinoid in mice
Chronic nicotine alters motivational value of natural rewards through circuit-based alterations in VTA dopamine neurons
Impact of the gut microbiota on nicotine effects and glia within the reward system in mice
The interpeduncular nucleus acts as a key modulator between reinforcement and aversive circuits in nicotine intake
Nicotine effects on anxiety behavior and brain biochemical markers in adult male mice and in rat hippocampal slices: patch clamp recordings
Phencyclidine and nicotine interactive effects in an adolescent mouse model of schizophrenia-like psychosis and nicotine misuse co-morbidity
Poor attentional control as a biomarker of vulnerability to nicotine addiction in male but not in female mice
Prenatal hypoxia related disturbances in glucocorticoid-dependent gene expression of chrna7 and genes of glutamate system are possible mechanism of development of nicotine addiction
Striatal cholinergic interneurons control nicotine withdrawal via muscarinic signaling
Unique gene expression profiles in the extinction of cocaine and nicotine self-administration
Exploring the neuroprotective effects of nicotine against MPTP-induced neuronal damage in mice: Insights into antioxidant system
FENS Forum 2024
Lavandula angustifolia or astrocytes alleviate nicotine plus high glucose-induced intracellular Ca2+ elevation in neurons and microglia
FENS Forum 2024
Nicotine biases motivational valence by altering brainstem cholinergic signals
FENS Forum 2024
Nicotine exposure during adolescence disrupts the dopaminergic circuitry in the ventral tegmental area
FENS Forum 2024
Nicotine suppresses feeding behavior by exerting opposite effects on the neuronal activity of the arcuate nucleus
FENS Forum 2024
Precise spatiotemporal photorelease of a systemically administered caged nicotine agonist in freely moving mice
FENS Forum 2024
Prenatal hypoxia, maternal stress, and the impact on CHRNA7 gene expression: Linking to nicotine addiction in adult offspring
FENS Forum 2024
Role of the interneurons in prefrontal-based attentional dysfunctions in nicotine addiction
FENS Forum 2024
Understanding the influence of the gut microbiome on the mesolimbic system and its response to nicotine
FENS Forum 2024
Understanding the neurobiological basis of the rewarding properties of flavored nicotine in e-cigarettes
FENS Forum 2024
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