ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Nicotine pharmacokinetics in rats is altered as a function of age, impacting the interpretation of animal model data.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- β-Nicotyrine and e-cigarette abuse liability I: Pharmacodynamics and interaction with pharmacokinetics and discriminative stimulus effects of nicotine in rats.Drug and alcohol dependence · 2025Article
- Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice.Neuropharmacology · 2025Article
- Behavioral and Pharmacokinetic Assessment of Nicotine e-Cigarette Inhalation in Female Rats.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Withdrawal from repeated nicotine vapor exposure increases somatic signs of physical dependence, anxiety-like behavior, and brain reward thresholds in adult male rats.Neuropharmacology · 2023Article
- β2 nAChR Activation on VTA DA Neurons Is Sufficient for Nicotine Reinforcement in Rats.eNeuro · 2023Article
- Chronic exposure to cigarette smoke extract increases nicotine withdrawal symptoms in adult and adolescent male rats.Advances in drug and alcohol research · 2023Article
- Relapse-like behavior and nAChR sensitization following intermittent access nicotine self-administration.Neuropharmacology · 2022Article
- Effects of excessive alcohol drinking on nicotine biotransformation in rats.Scientific reports · 2022Article
- Biological determinants impact the neurovascular toxicity of nicotine and tobacco smoke: A pharmacokinetic and pharmacodynamics perspective.Neurotoxicology · 2022Review
- The involvement of mesolimbic dopamine system in cotinine self-administration in rats.Behavioural brain research · 2022Article
- Rodent models for nicotine withdrawal.Journal of psychopharmacology (Oxford, England) · 2021Review
- Inactivation of posterior but not anterior dorsomedial caudate-putamen impedes learning with self-administered nicotine stimulus in male rats.Behavioural brain research · 2021Article
- Differential effects of alkaloids on memory in rodents.Scientific reports · 2021Article
- Physiologically Based Pharmacokinetic Modelling for Nicotine and Cotinine Clearance in Pregnant Women.Frontiers in pharmacology · 2021Article
- Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions.Frontiers in behavioral neuroscience · 2021Review
- Unique, long-term effects of nicotine on adolescent brain.Pharmacology, biochemistry, and behavior · 2020Review
- Adolescent nicotine and tobacco smoke exposure enhances nicotine self-administration in female rats.Neuropharmacology · 2020Article
- High-dose adolescent nicotine exposure permits spontaneous nicotine self-administration in adult male rats.Drug and alcohol dependence · 2020Article
- Effects of nicotine, nornicotine and cotinine, alone or in combination, on locomotor activity and ultrasonic vocalization emission in adult rats.Psychopharmacology · 2020Article
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6 authors.
Funding
Abstract
Several behavioral studies report that adolescent rats display a preference for nicotine compared with adults. However, age-related pharmacokinetic differences may confound the interpretation of these findings. Thus, differences in pharmacokinetic analyses of nicotine were investigated. Nicotine was administered via acute s.c. (1.0 mg base/kg) or i.v. (0.2 mg base/kg) injection to early adolescent (EA; postnatal day 25) and adult (AD; postnatal day 71) male Wistar rats. Nicotine and its primary metabolite, cotinine, and additional metabolites nornicotine, nicotine-1'-N-oxide, trans-3'-hydroxycotinine, and norcotinine were sampled from 10 minutes to 8 hours (plasma) and 2 to 8 hours (brain) post nicotine and analyzed by liquid chromatography-tandem mass spectrometry. Following s.c. nicotine, the EA cohort had lower levels of plasma nicotine, cotinine, and nicotine-1'-N-oxide at multiple time points, resulting in a lower area under the plasma concentration-time curve (AUC) for nicotine (P < 0.001), cotinine (P < 0.01), and nicotine-1'-N-oxide (P < 0.001). Brain levels were also lower for these compounds. In contrast, the EA cohort had higher plasma and brain AUCs (P < 0.001) for the minor metabolite nornicotine. Brain-to-plasma ratios varied for nicotine and its metabolites, and by age. Following i.v. nicotine administration, similar age-related differences were observed, and this route allowed detection of a 1.6-fold-larger volume of distribution and 2-fold higher plasma clearance in the EA cohort compared with the AD cohort. Thus, unlike in humans, there are substantial age differences in nicotine pharmacokinetics such that for a given nicotine dose, adolescent rats will have lower plasma and brain nicotine compared with adults, suggesting that this should be considered when interpreting animal model data.
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