Serotonergic neurons mediate ectopic release of dopamine induced by l-DOPA in a rat model of Parkinson's disease

Autor: Sylvia Navailles, Bernard Bioulac, Christian Gross, Philippe De Deurwaerdère
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Neurobiology of Disease, Vol 38, Iss 1, Pp 136-143 (2010)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2010.01.012
Popis: 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.
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