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Abstract
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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