Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration
| Autor: | Rachel F. Tyndale, Kristine L. P. Garcia, Anh D. Lê, Sharon Miksys, Kathy Coen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Microdialysis Nicotine Time Factors CYP2B6 Self Administration Pharmacology Extinction Psychological chemistry.chemical_compound In vivo Medicine Animals Cytochrome P-450 Enzyme Inhibitors Nicotinic Agonists Cotinine Injections Intraventricular Dose-Response Relationship Drug business.industry Brain Thiones Rats Psychiatry and Mental health Nicotinic agonist chemistry Conditioning Operant Original Article Self-administration business Reinforcement Psychology Drug metabolism medicine.drug |
| Popis: | The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotine-mediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC0–45min were both twofold higher (p |
| Databáze: | OpenAIRE |
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