Biology subjects

Chellian, R. k.

Publications and source records attributed to Chellian, R. k..

3 recordsLinked to original sources

bioRxiv2026

Dissociable roles of dopamine D1 and nicotinic receptors in nicotine-motivated responding and impulsive action in a Go/No-Go self-administration task

Cigarette smoking remains one of the most important preventable causes of premature death worldwide. However, the mechanisms sustaining nicotine dependence and relapse are incompletely understood, particularly the role of impulsive action in persistent tobacco use. Dopamine D1 and nicotinic acetylcholine receptors both regulate nicotine-related behavior, but whether they contribute differently to nicotine-motivated responding and nicotine-induced impulsive action is unclear. The present study examined the effects of D1 receptor blockade and stimulation in male and female rats trained to self-administer nicotine intravenously in a Go/No- Go task. Nicotine was available during Go periods but not during No-Go periods, and impulsive action was measured as the percentage of active lever responses during No-Go periods. The D1 receptor antagonist SCH23390 reduced nicotine intake and active lever responding during Go periods and affected the percentage of active lever responses during No-Go periods. However, SCH23390 also reduced inactive lever responding, so its effect on impulsive action could not be separated from a general reduction in operant output. In contrast, the D1 receptor agonist A77636 reduced nicotine intake and Go-period responding without affecting No-Go responding, indicating that D1 receptor stimulation reduced nicotine-motivated responding without altering impulsive action. Rats showed greater No-Go responding during nicotine self-administration than during saline self-administration, indicating that nicotine increased impulsive action rather than general operant responding. The non-selective nicotinic antagonist mecamylamine reduced nicotine-motivated responding and decreased No-Go responding, indicating reduced impulsive action. These findings suggest that nicotinic acetylcholine receptor signaling plays a major role in nicotine-induced impulsive action, whereas D1 receptor signaling contributes more clearly to nicotine-motivated responding. D1 receptor agonism may reduce nicotine-motivated behavior without affecting nicotine-induced impulsive action.

neuroscience↗

bioRxiv2024

AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 - 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/599576v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1f6ee4corg.highwire.dtl.DTLVardef@96e062org.highwire.dtl.DTLVardef@16579a0org.highwire.dtl.DTLVardef@1140a8e_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

Mifepristone decreases nicotine intake in dependent and non-dependent adult rats

Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new treatments to reduce tobacco and nicotine use. Glucocorticoid receptor blockade shows promise as a novel treatment for drug abuse and stress-related disorders. The aim of these studies was to investigate if glucocorticoid receptor blockade with mifepristone diminishes the reinforcing properties of nicotine in rats with intermittent or daily long access to nicotine. The rats self-administered 0.06 mg/kg/inf of nicotine for 6 h per day, with either intermittent (3 days per week) or daily access (7 days per week) for 4 weeks before treatment with mifepristone. Daily nicotine self-administration models regular smoking, while intermittent nicotine self-administration models occasional smoking. To determine if the rats were dependent, they were treated with the nicotinic acetylcholine receptor antagonist mecamylamine, and somatic signs were recorded. The rats with intermittent access to nicotine had a higher level of nicotine intake per session than those with daily access, but only the rats with daily access to nicotine showed signs of dependence. Furthermore, mecamylamine increased nicotine intake during the first hour of access in rats with daily access but not in those with intermittent access. Mifepristone decreased total nicotine intake in rats with intermittent and daily access to nicotine. Moreover, mifepristone decreased the total distance traveled and rearing in the open field test and operant responding for food pellets. These findings indicate that mifepristone decreases the reinforcing effects of nicotine and food, but it might also be somewhat sedative.

pharmacology and toxicology↗