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In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone

RATIONALE: 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 nic...

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Autores principales: Budzynska, Barbara, Skalicka-Wozniak, Krystyna, Kruk-Slomka, Marta, Wydrzynska-Kuzma, Malgorzata, Biala, Grazyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873531/
https://www.ncbi.nlm.nih.gov/pubmed/27080866
http://dx.doi.org/10.1007/s00213-016-4279-9
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author Budzynska, Barbara
Skalicka-Wozniak, Krystyna
Kruk-Slomka, Marta
Wydrzynska-Kuzma, Malgorzata
Biala, Grazyna
author_facet Budzynska, Barbara
Skalicka-Wozniak, Krystyna
Kruk-Slomka, Marta
Wydrzynska-Kuzma, Malgorzata
Biala, Grazyna
author_sort Budzynska, Barbara
collection PubMed
description RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-48735312016-06-21 In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone Budzynska, Barbara Skalicka-Wozniak, Krystyna Kruk-Slomka, Marta Wydrzynska-Kuzma, Malgorzata Biala, Grazyna Psychopharmacology (Berl) Original Investigation RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Springer Berlin Heidelberg 2016-04-14 2016 /pmc/articles/PMC4873531/ /pubmed/27080866 http://dx.doi.org/10.1007/s00213-016-4279-9 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Investigation
Budzynska, Barbara
Skalicka-Wozniak, Krystyna
Kruk-Slomka, Marta
Wydrzynska-Kuzma, Malgorzata
Biala, Grazyna
In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
title In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
title_full In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
title_fullStr In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
title_full_unstemmed In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
title_short In vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
title_sort in vivo modulation of the behavioral effects of nicotine by the coumarins xanthotoxin, bergapten, and umbelliferone
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873531/
https://www.ncbi.nlm.nih.gov/pubmed/27080866
http://dx.doi.org/10.1007/s00213-016-4279-9
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