Noradrenergic terminals regulate L-DOPA-derived dopamine extracellular levels in a region-dependent manner in Parkinsonian rats.
CNS Neurosci Ther. 2014-04-28; 20(7): 671-678
DOI: 10.1111/cns.12275
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AIMS: Serotonin (5-HT) neurons mediate the ectopic release of dopamine (DA)
induced by L-DOPA in the Parkinsonian brain. We hypothesized that the
participation of noradrenalin transporters (NET) in the clearance of DA may
account for the lower effect of L-DOPA in extrastriatal regions compared with the
striatum.
METHODS: Using a multisite intracerebral microdialysis approach, we tested the
influence of the pharmacological blockade of NET and/or the destruction of
noradrenalin (NE) fibers on DA and 5-HT release in the striatum, hippocampus
(HIPP), substantia nigra pars reticulata (SNr) and prefrontal cortex (PFC) of
6-hydroxydopamine-lesioned rats.
RESULTS: L-DOPA (12 mg/kg, i.p.) increased DA extracellular levels to a lesser
extent in the SNr, PFC and HIPP compared with the striatum. The NET blockers
desipramine (10 mg/kg, i.p.) and reboxetine (3 mg/kg, i.p.) potentiated L-DOPA
effect in the PFC, SNr and HIPP but not in the striatum. The NE neurotoxin
N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg, i.p. 1 week before
dialysis experiment) potentiated L-DOPA effect in the SNr and HIPP. 5-HT
extracellular levels were enhanced only when L-DOPA was combined to NET blockers.
CONCLUSION: Noradrenalin neurons are indirectly involved in the mechanism of
action of L-DOPA in part through the heterologous reuptake of DA in extrastriatal
regions.
© 2014 John Wiley & Sons Ltd.