Noradrenergic Terminals Regulate l- DOPA-derived Dopamine Extracellular Levels in a Region-dependent Manner in Parkinsonian Rats.

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. [ABSTRACT FROM AUTHOR]