title: In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone.
abstract: Nicotine, a dominant alkaloid found in tobacco, is responsible for physical dependence, as well as addiction to cigarette smoking; consequently, smoking cessation is a very difficult process. Hepatic cytochrome P-450 2A6 (CYP2A6) is involved in the 70-80 % of the initial metabolism of nicotine and its co-metabolites. As this metabolism is slowed by inhibitors of CYP2A6, this kind of enzymatic inhibition has been proposed as a novel target for smoking cessation.
  
  
  
  Nicotine administered alone improved memory acquisition and consolidation as well as exerted antidepressive activity in animal models. These effects persist for 24 h. However, they are completely extinguished 48 h after administration.
  
  
  
  To investigate if the coumarins prolong the behavioral effects of nicotine, the forced swimming test (FST)-animal models of depression, and passive avoidance (PA) test-memory and learning paradigm were used.
  
  
  
  This study revealed that three CYP2A6 inhibitors: two furanocoumarins, xanthotoxin (15 mg/kg) and bergapten (25 mg/kg), and the simple coumarin umbelliferone (25 mg/kg), prolonged the antidepressive and procognitive effects of nicotine.
  
  
  
  These natural products may offer a new approach to the treatment of nicotinism as antidepressant and memory improvement actions are one of the main factors of nicotine dependence.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland. basia.budzynska@umlub.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Budzynska
authors.affiliation: Department of Pharmacognosy with Medicinal Plants Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Skalicka-Wozniak
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kruk-Slomka
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wydrzynska-Kuzma
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Biala
mesh_terms: D000078223:5-Methoxypsoralen; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology*; D065637:Cytochrome P-450 CYP2A6 / Q000037:antagonists & inhibitors; D003863:Depression / Q000523:psychology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D003374:Coumarins; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D014468:Umbelliferones; D000078223:5-Methoxypsoralen; C031477:7-hydroxycoumarin; D009538:Nicotine; D065637:Cytochrome P-450 CYP2A6; D008730:Methoxsalen
keywords: Coumarins; Depression; Memory; Mice; Nicotine