L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.
Identifieur interne : 001562 ( Main/Curation ); précédent : 001561; suivant : 001563L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.
Auteurs : Sylvia Navailles [France] ; Manolo Carta ; Martin Guthrie ; Philippe De DeurwaerdèreSource :
- Central nervous system agents in medicinal chemistry [ 1875-6166 ] ; 2011.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (metabolism), Antiparkinson Agents (pharmacology), Antiparkinson Agents (therapeutic use), Dopamine (metabolism), Humans, Levodopa (metabolism), Levodopa (pharmacology), Levodopa (therapeutic use), Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Serotonergic Neurons (drug effects), Serotonergic Neurons (metabolism), Serotonin (metabolism).
- MESH :
- chemical , metabolism : Antiparkinson Agents, Dopamine, Levodopa, Serotonin.
- chemical , pharmacology : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- drug effects : Serotonergic Neurons.
- drug therapy : Parkinson Disease.
- metabolism : Parkinson Disease, Serotonergic Neurons.
- Animals, Humans.
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.
PubMed: 22117594
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xml:lang="fr">France</country><wicri:regionArea>Université de Bordeaux, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5293, 33076 Bordeaux cedex</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Carta, Manolo" sort="Carta, Manolo" uniqKey="Carta M" first="Manolo" last="Carta">Manolo Carta</name></author><author><name sortKey="Guthrie, Martin" sort="Guthrie, Martin" uniqKey="Guthrie M" first="Martin" last="Guthrie">Martin Guthrie</name></author><author><name sortKey="De Deurwaerdere, Philippe" sort="De Deurwaerdere, Philippe" uniqKey="De Deurwaerdere P" first="Philippe" last="De Deurwaerdère">Philippe De Deurwaerdère</name></author></analytic><series><title level="j">Central nervous system agents in medicinal 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type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Serotonergic Neurons</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term><term>Serotonergic Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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