cobrotoxin and Parkinsonian-Disorders

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.

Topics: 5,7-Dihydroxytryptamine; Animals; Antiparkinson Agents; Brain; Citalopram; Cobra Neurotoxin Proteins; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Extracellular Fluid; Levodopa; Male; Microdialysis; Oxidopamine; Parkinsonian Disorders; Presynaptic Terminals; Raphe Nuclei; Rats; Selective Serotonin Reuptake Inhibitors; Serotonin; Sympatholytics; Synaptic Transmission