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

Sylvia Navailles, Bernard Bioulac, Christian Gross, Philippe De Deurwaerdère
Neurobiology of Disease. 2010-04-01; 38(1): 136-143
DOI: 10.1016/j.nbd.2010.01.012

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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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