NICPARK · Characterization of the neurobiological processes underlying the antiparkinsonian effects of nicotine

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Project objective

Epidemiological studies indicate that cigarette smoking protects from Parkinson's disease (PD), and a recent unpublished clinical study has shown that progressively increasing doses of nicotine improve the symptoms of PD and allow patients to dramatically reduce their dosages of L-DOPA, the most widely used anti-PD treatment. How nicotine may interact with L-DOPA to enhance functioning in PD, however, remains unknown. In preliminary studies using an animal model of PD, Sokoloff and colleagues have recently found that nicotine's ability to enhance sensitivity to L-DOPA involves an increase in the expression of brain-derived neurotrophic factor and of the dopamine D3 receptor in specific brain regions.The aim of the current project is to extend these findings and to determine the precise neurobiological mechanisms that may underlie the anti-parkinsonian properties of nicotine. To this end, behavioural, pharmacological, and electrophysiological approaches will be used to investigate the effects of repeated nicotine treatment in parkinsonian-like animals. In addition, selective pharmacological agents and mouse lines deficient in specific nicotinic receptor subunits will be used to identify the nicotinic receptor subtypes necessary for the therapeutic effects of nicotine. We expect these results to contribute to the development of new selective nicotinic therapeutic agents for the treatment of PD, and thereby directly benefit patients suffering from PD.The project will be undertaken by a Canadian post-doctoral re searcher whose doctoral training at the University of Michigan (USA) has endowed her with excellent research skills and a number of publications in top-rated scientific journals. By supporting this and other international researchers, the European Commission will help to counter the brain-drain" of European scientists towards American laboratories."

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Participants

• INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · PARISCoordinatorFrance

Links

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