ArticleNeuropharmacology2014
Effects of methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice.
Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- β-Nicotyrine and e-cigarette abuse liability II: Behavioral economic demand and intracranial self-stimulation in rats.Drug and alcohol dependence · 2026Article
- The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.Molecular neurobiology · 2024Article
- Methoxsalen Inhibits the Acquisition of Nicotine Self-Administration: Attenuation by Cotinine Replacement in Male Rats.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers.Pharmacology research & perspectives · 2023Article
- Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.Frontiers in pharmacology · 2023Article
- Pharmacokinetic differences in nicotine and nicotine salts mediate reinforcement-related behavior: an animal model study.Frontiers in neuroscience · 2023Article
- Genetic differences in nicotine sensitivity and metabolism in C57BL/6J and NOD/ShiLtJ mouse strains.Neuropharmacology · 2022Article
- Non-nicotine constituents in cigarette smoke extract enhance nicotine addiction through monoamine oxidase A inhibition.Frontiers in neuroscience · 2022Article
- Nicotine and Its Downstream Metabolites in Maternal and Cord Sera: Biomarkers of Prenatal Smoking Exposure Associated with Offspring DNA Methylation.International journal of environmental research and public health · 2020Article
- Advances in smoking cessation pharmacotherapy: Non-nicotinic approaches in animal models.Neuropharmacology · 2020Review
- The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice.The Journal of pharmacology and experimental therapeutics · 2020Article
- Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice.Biopharmaceutics & drug disposition · 2019Article
- Cytochrome P450: Polymorphisms and Roles in Cancer, Diabetes and AtherosclerosisAsian Pacific journal of cancer prevention : APJCP · 2018Review
- Identification of the 4-Position of 3-Alkynyl and 3-Heteroaromatic Substituted Pyridine Methanamines as a Key Modification Site Eliciting Increased Potency and Enhanced Selectivity for Cytochrome P-450 2A6 Inhibition.Journal of medicinal chemistry · 2018Article
- Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.The Journal of pharmacology and experimental therapeutics · 2018Article
- In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.Neuropharmacology · 2017Article
- An Inventory of Methods for the Assessment of Additive Increased Addictiveness of Tobacco Products.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016Review
- In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone.Psychopharmacology · 2016Article
- Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers.Drug and alcohol dependence · 2016Article
- Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the principal pathway by which active nicotine is removed from circulation. We therefore hypothesized that inhibition of mouse CYP2A5, the ortolog of human CYP2A6, by methoxsalen (8-methoxypsoralen) alter dependence-related behaviors of nicotine in the mouse. Conditioned place preference (CPP) test was used to assess the appetitive reward-like properties and precipitated nicotine withdrawal to assess physical (somatic and hyperalgesia) and affective (anxiety-related behaviors) measures. The nicotine plasma levels were also measured with or without methoxsalen pretreatment. Methoxsalen (15 and 30 mg/kg, intraperitoneally) pretreatment enhanced nicotine-induced preference in mice (p<0.05). However, there was a lack of enhancement of nicotine in the CPP test after the highest dose of the CYP-2A5 inhibitor. Similarly to the CPP results, repeated administration of methoxsalen increased the intensity of mecamylamine-precipitated withdrawal signs. The potentiation of nicotine preference and withdrawal intensity by methoxsalen was accompanied by significant increase in nicotine plasma levels in mice (p<0.05). Finally, methoxsalen enhanced the ability of a very low dose of nicotine (0.05 mg/kg) to reverse withdrawal signs in mice undergoing spontaneous withdrawal after chronic nicotine infusion (p<0.05). In conclusion, inhibition of nicotine metabolism by methoxsalen alters the behavioral effects of nicotine in the mouse. Combining CYP2A6 inhibitors with low dose nicotine replacement therapies may have a beneficial role in smoking cessation because it will decrease the drug elimination rate and maintain plasma and brain nicotine levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.