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High Reinforcing Efficacy of Nicotine in Non-Human Primates

Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of et...

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Autores principales: Le Foll, Bernard, Wertheim, Carrie, Goldberg, Steven R.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794142/
https://www.ncbi.nlm.nih.gov/pubmed/17311094
http://dx.doi.org/10.1371/journal.pone.0000230
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author Le Foll, Bernard
Wertheim, Carrie
Goldberg, Steven R.
author_facet Le Foll, Bernard
Wertheim, Carrie
Goldberg, Steven R.
author_sort Le Foll, Bernard
collection PubMed
description Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule) or increased progressively with successive injections during the session (progressive-ratio schedule), allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys' behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence.
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spelling pubmed-17941422007-02-21 High Reinforcing Efficacy of Nicotine in Non-Human Primates Le Foll, Bernard Wertheim, Carrie Goldberg, Steven R. PLoS One Research Article Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule) or increased progressively with successive injections during the session (progressive-ratio schedule), allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys' behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence. Public Library of Science 2007-02-21 /pmc/articles/PMC1794142/ /pubmed/17311094 http://dx.doi.org/10.1371/journal.pone.0000230 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Le Foll, Bernard
Wertheim, Carrie
Goldberg, Steven R.
High Reinforcing Efficacy of Nicotine in Non-Human Primates
title High Reinforcing Efficacy of Nicotine in Non-Human Primates
title_full High Reinforcing Efficacy of Nicotine in Non-Human Primates
title_fullStr High Reinforcing Efficacy of Nicotine in Non-Human Primates
title_full_unstemmed High Reinforcing Efficacy of Nicotine in Non-Human Primates
title_short High Reinforcing Efficacy of Nicotine in Non-Human Primates
title_sort high reinforcing efficacy of nicotine in non-human primates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794142/
https://www.ncbi.nlm.nih.gov/pubmed/17311094
http://dx.doi.org/10.1371/journal.pone.0000230
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