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The Journal of Neuroscience, January 28, 2009, 29(4):987-997; doi:10.1523/JNEUROSCI.3315-08.2009
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Behavioral/Systems/Cognitive
Inhibition of Monoamine Oxidases Desensitizes 5-HT1A Autoreceptors and Allows Nicotine to Induce a Neurochemical and Behavioral Sensitization
Christophe Lanteri,1,2 Sandra Jimena Hernández Vallejo,2,3 Lucas Salomon,1,2 Emilie Lucie Doucet,1,2 Gérard Godeheu,1 Yvette Torrens,1 Vanessa Houades,1 andJean-Pol Tassin1 1Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7148, Collège de France, and 2Université Pierre et Marie Curie, Université Paris 06, F-75005 Paris, France, and 3Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S893, Equipe 9, Faculté de Médecine Pierre et Marie Curie, Site Saint Antoine, F-75012 Paris, France
Correspondence should be addressed to Jean-Pol Tassin, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7148, Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France. Email: jean-pol.tassin{at}college-de-france.fr
Although nicotine is generally considered to be the main compound responsible for addictive properties of tobacco, experimental data indicate that nicotine does not exhibit all the characteristics of other substances of abuse. We recently showed that a pretreatment with mixed irreversible monoamine oxidases inhibitors (MAOIs), such as tranylcypromine, triggers a locomotor response to nicotine in mice and allows maintenance of behavioral sensitization to nicotine in rats. Moreover, we showed by microdialysis in mice that behavioral sensitization induced by compounds belonging to main groups of drugs of abuse, such as amphetamine, cocaine, morphine, or alcohol, was underlain by sensitization of noradrenergic and serotonergic neurons. Here, this neurochemical sensitization was tested after nicotine, tranylcypromine, or a mixture of both compounds. Data indicate that, whereas neither repeated nicotine nor repeated tranylcypromine alone has any effect by itself, a repeated treatment with a mixture of nicotine and tranylcypromine induces both behavioral sensitization and sensitization of noradrenergic and serotonergic neurons. The development of neurochemical and behavioral sensitizations is blocked by prazosin and SR46349B [(1Z,2E)-1-(2-fluoro-phenyl)-3-(4-hydroxyphenyl)-prop-2-en-one-O-(2-dimethylamino-ethyl)-oxime hemifumarate], two antagonists of
1b-adrenergic and 5-HT2A receptors, respectively, but not by SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride], a D1 receptor antagonist. Finally, we found that pretreatments with WAY 100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide trihydrochloride], a 5-HT1A receptor antagonist, can also induce a behavioral and neurochemical sensitization to repeated nicotine. Complementary experiments with 8-OHDPAT (8-hydroxy-dipropylamino-tetralin), a 5-HT1A receptor agonist, and analysis of 5-HT1A receptors expression in the dorsal raphe nucleus after a tranylcypromine injection indicate that MAOIs contained in tobacco desensitize 5-HT1A autoreceptors to trigger the strong addictive properties of tobacco.
Key words: 5-HT2A serotonergic receptor;
Received July 16, 2008; revised Dec. 15, 2008; accepted Dec. 15, 2008.
Correspondence should be addressed to Jean-Pol Tassin, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7148, Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France. Email: jean-pol.tassin{at}college-de-france.fr
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