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Modifications à long terme des systèmes noradrénergique et sérotoninergique dans la sensibilisation comportementale induite par l'éthanol et l'amphétamine

Abstract : Our team studies the neurobiological changes induced by drugs of abuse through the behavioral sensitization model. This model is characterised, in rodents, by a progressively enhanced locomotor response to repeated exposures to drugs of abuse. We have previously shown that the behavioral sensitization to main classes of drugs of abuse (psychostimulants, opiates, alcohol or tobacco) observed in C57Bl/6J mice was underlined by a noradrenergic and a serotonergic neuronal sensitization. In my thesis, I first detail the pathway followed by ethanol to induce a noradrenergic neuronal sensitization. Our data have shown that the µ-opioid system is essential to induce this phenomenon. Actually, the blockade by naltrexone of µ-opioid receptors before ethanol injections prevents the development of ethanol behavioral sensitization. Moreover, µ-opioid receptors knock-out mice did not exhibit behavioral nor noradrenergic sensitization to ethanol although they were still responsive to sensitization induced by amphetamine. Secondly, we studied how the noradrenergic and serotonergic sensitization induced by amphetamine could persist after many months withdrawal. Electrophysiological recordings as well as micro-dialysis experiments showed that noradrenergic and serotonergic inhibitor feedbacks, composed by α2A-adrenergic and 5-HT1A auto-receptors respectively, were persistently impaired in rats and mice sensitized to amphetamine. This desensitization was correlated with a decreased expression of Gαi proteins coupled to these receptors.
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Submitted on : Friday, May 31, 2013 - 1:36:52 PM
Last modification on : Wednesday, December 23, 2020 - 11:28:06 AM

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  • HAL Id : tel-00828603, version 1

Citation

Emilie Doucet. Modifications à long terme des systèmes noradrénergique et sérotoninergique dans la sensibilisation comportementale induite par l'éthanol et l'amphétamine. Neurobiologie. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PA066385⟩. ⟨tel-00828603⟩

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