L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.

Sylvia Navailles 1 Manolo Carta Martin Guthrie 1 Philippe de Deurwaerdère 1
1 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
Abstract : L-DOPA is the gold standard medication of Parkinson's disease, a neurological disorder consequent upon the degeneration of mesencephalic dopaminergic neurons. The therapeutic efficacy of L-DOPA has been related to its ability to restore dopamine (DA) extracellular levels in the Parkinsonian brain. The origin of the L-DOPA-induced rise in DA has been the object of numerous studies and controversies but the data collectively point to serotonergic (5-HT) neurons as being most significant in the release. Here, we review biochemical and behavioral evidence supporting serotonergic neurons as playing the main role in the actions of L-DOPA, considered from two points of view. The main aspect concerns the biochemical demonstration that 5-HT neurons are almost solely implicated in the release of DA induced by L-DOPA. The mechanism of action of L-DOPA inside 5-HT neurons will be thoroughly dissected on the basis of L-DOPA effects on extracellular versus tissue DA levels. The unique contribution of 5-HT neurons in mediating the release of newly synthesised DA from L-DOPA will be discussed in parallel with DA-dependent behaviors induced by L-DOPA. The other, and neglected, aspect concerns the possible deleterious impact of the presence of L-DOPA inside 5-HT neurons on 5-HT neuronal function. Overall, the fact that 5-HT neurons release the newly synthesised DA from L-DOPA in multiple brain regions beyond the striatum gives new insight into the large impact of L-DOPA in the Parkinsonian brain and strengthens therapeutic perspectives targeting the 5-HT system to reduce both motor and non-motor complications of L-DOPA medication.
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https://hal.archives-ouvertes.fr/hal-01178542
Contributeur : Philippe de Deurwaerdere <>
Soumis le : lundi 20 juillet 2015 - 13:16:26
Dernière modification le : jeudi 11 janvier 2018 - 06:25:41

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  • HAL Id : hal-01178542, version 1
  • PUBMED : 22117594

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Sylvia Navailles, Manolo Carta, Martin Guthrie, Philippe de Deurwaerdère. L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.. Central Nervous System Agents in Medicinal Chemistry, Bentham Science Publishers, 2011, 11 (4), pp.305-20. ⟨hal-01178542⟩

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