Serotonergic neurons mediate ectopic release of dopamine induced by L-DOPA in a rat model of Parkinson's disease.
Benefit and motor side effects of l-DOPA in Parkinson's disease have been related to dopamine transmission in the striatum. However, the putative involvement of serotonergic neurons in the dopaminergic effects of l-DOPA suggests that the striatum is not a preferential target of l-DOPA. By using microdialysis in a rat model of Parkinson's disease, we found that l-DOPA (3-100 mg/kg) increased dopamine extracellular levels monitored simultaneously in four brain regions receiving serotonergic innervation: striatum, substantia nigra, hippocampus, prefrontal cortex. The increase was regionally similar at the lowest dose and 2-3 times stronger in the striatum at higher doses. Citalopram, a serotonin reuptake blocker, or the destruction of serotonergic fibers by 5,7-dihydroxytryptamine impaired l-DOPA-induced dopamine release in all regions. These data demonstrate that l-DOPA induces an ectopic release of dopamine due to serotonergic neurons. The new pattern of dopamine transmission created by l-DOPA may contribute to the benefit and side effects of l-DOPA.
Navailles
Sylvia
S
Université de Bordeaux, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5227, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux cedex, France.
Bioulac
Bernard
B
Gross
Christian
C
De Deurwaerdère
Philippe
P
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D003039:Cobra Neurotoxin Proteins / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013565:Sympatholytics; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015116:5,7-Dihydroxytryptamine; D000978:Antiparkinson Agents; D015283:Citalopram; D003039:Cobra Neurotoxin Proteins; D004298:Dopamine; D007980:Levodopa; D016627:Oxidopamine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013565:Sympatholytics; C111881:neurotoxin 12-1