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The Journal of Neuroscience, September 21, 2005, 25(38):8593-8600; doi:10.1523/JNEUROSCI.2139-05.2005

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Behavioral/Systems/Cognitive
Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats

Karine Guillem,¹ Caroline Vouillac,¹ Marc R. Azar,² Loren H. Parsons,² George F. Koob,² Martine Cador,¹ and Luis Stinus¹

¹Laboratoire de Neuropsychobiologie des Désadaptations, Unité Mixte de Recherche 5541, Centre National de la Recherche Scientifique, Universitéde Bordeaux 2, 33076 Bordeaux Cedex, France, and ²Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Nicotine is the major neuroactive compound of tobacco, which has, by itself, weak reinforcing properties. It is known that levels of the enzymes monoamine oxidase A (MAO-A) and MAO-B are reduced in the platelets and brains of smokers and that substances, other than nicotine, present in tobacco smoke have MAO-inhibitory activities. Here, we report that inhibition of MAO dramatically and specifically increases the motivation to self-administer nicotine in rats. These effects were more prominent in rats selected for high responsiveness to novelty than in rats with low responsiveness to novelty. The results suggest that the inhibition of MAO activity by compounds present in tobacco smoke may combine with nicotine to produce the intense reinforcing properties of cigarette smoking that lead to addiction.

Key words: nicotine self-administration; tranylcypromine; phenelzine; high and low responders; fixed ratio; progressive ratio

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Received March 3, 2005; revised August 3, 2005; accepted August 4, 2005.

This article has been cited by other articles:

				S. Caille, K. Guillem, M. Cador, O. Manzoni, and F. Georges Voluntary Nicotine Consumption Triggers In Vivo Potentiation of Cortical Excitatory Drives to Midbrain Dopaminergic Neurons J. Neurosci., August 19, 2009; 29(33): 10410 - 10415. [Abstract] [Full Text] [PDF]

				C. Lanteri, S. J. Hernandez Vallejo, L. Salomon, E. L. Doucet, G. Godeheu, Y. Torrens, V. Houades, and J.-P. Tassin Inhibition of Monoamine Oxidases Desensitizes 5-HT1A Autoreceptors and Allows Nicotine to Induce a Neurochemical and Behavioral Sensitization J. Neurosci., January 28, 2009; 29(4): 987 - 997. [Abstract] [Full Text] [PDF]

				M. De Biasi and R. Salas Influence of Neuronal Nicotinic Receptors over Nicotine Addiction and Withdrawal Experimental Biology and Medicine, August 1, 2008; 233(8): 917 - 929. [Abstract] [Full Text] [PDF]

				S. Agatsuma, M. Lee, H. Zhu, K. Chen, J. C. Shih, I. Seif, and N. Hiroi Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli Hum. Mol. Genet., September 15, 2006; 15(18): 2721 - 2731. [Abstract] [Full Text] [PDF]

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