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PSN

, Volume 1, Issue 3, pp 13–18 | Cite as

Rôle des systèmes de recapture dopaminergiques dans la physiopathologie de l’addiction

  • Bruno Giros
Neurosciences

Résumé

Le transporteur de la dopamine est une protéine essentielle pour la dynamique de la neurotransmission de cette catécholamine. Localisé dans la membrane présynaptique, il assure une recapture rapide et efficace de la dopamine libérée, contrôlant ainsi de façon précise la concentration dopaminergique, à la fois dans le temps et dans l’espace. Ce rôle est mis en évidence de manière intégrée par l’action de psychotropes qui vont bloquer son activité, comme les psychostimulants (cocaine, amphétamine), dont les effets comportementaux sont extraordinairement puissants. Cette protéine a été clonée et caractérisée au début des années 1990. Nous passerons en revue les caractéristiques moléculaires du transporteur de la dopamine et les relations structures-activités déduites des études pharmacologiques sur des transporteurs exprimés in vitro dans des systèmes cellulaires. La fabrication d’un modèle animal chez la souris, avec une délétion du gène codant pour ce transporteur a permis de révéler le rôle dynamique de ce transporteur, et d’en déduire la fonction de la transmission dopaminergique dans un grand nombre de situations, du physiologique jusqu’au pathologique. Nous nous focaliserons içi principalement sur les comportements addictifs. Finalement, le clonage du gène humain a permis de conduire des études de génétique, qui ont aussi impliqué ce transporteur dans la vulnérabilité aux conduites addictives, principalement pour l’alcool et la cigarette. Bien que de nombreuses recherches doivent encore être menées chez l’homme et chez l’animal, ce que nous avons déjà appris reste un exemple parfait de l’interfécondité des études cliniques et fondamentales pour la compréhension des pathologies psychiatriques, ou nous avons besoin de comprendre le fonctionnement cérébral depuis les aspects moléculaires jusqu’aux fonctions intégrées supérieures.

Mots Clés

Transporteur de la dopamine Addiction 

The dopamine transporter is intimately linked to the dynamic of dopamine transmission: Role in addictive behaviors

Abstract

The dopamine transporter is essential to control the dynamic of dopamine transmission. Localized at the presynaptic membrane, these transporters ensure the rapid and efficient reuptake of released dopamine, therefore regulating dopamine concentration both in time and space. This role is highlighted with the use of reuptake inhibitors, like the psychostimulants cocaine and amphetamine, which displayed profound behavioral effects in animals and humans. The dopamine transporter was clone in the early 90’s, and much was learned in term of structure-activity relationships from in vitro models. A mouse model with a genetic disruption of the dopamine transporter gene was engineered, unraveling its role in the dynamic of dopamine neurotransmission, in various physiological conditions from the normal to the pathologic. Finally, cloning of the human gene allowed conducting genetic studies, which implicated the dopamine transporter in the vulnerability to some addictive behaviors, mainly cigarette smoking and drinking behavior. Obviously, even if we still have a lot to learn from human and animal studies, this work on the dopamine transporter is a perfect example of the cross-fecundity between these two aspects of research aiming at a better understanding of pscyhiatric disorders. It clearly shows that we have to understanding brain functions not only from a single angle, but from molecular to integrated and cognitive aspects.

Keywords

Dopamine transporter Addiction 

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Copyright information

© Springer 2003

Authors and Affiliations

  1. 1.Inserm U513Faculté de MédecineCréteil

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