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. (C) 2010 Elsevier Inc. All rights reserved.