|M.Sc Student||Dayan Lior|
|Subject||L-DOPA Induced Noradrenaline Release in the Central and|
Peripheral Nervous Systems
|Department||Department of Medicine||Supervisor||Professor Emeritus John Finberg|
There is a substantial decrease in NA concentration in certain brain areas in PD patients (as compared with healthy controls), e.g. frontal cortex and locus ceruleus. Research goals were to study the effects of L-DOPA on extracellular NA levels and release in the central and peripheral noradrenergic neuronal systems. Electrical field-stimulation (EFS) induced contractions in the epididymal portion of the rat vas deferens were used to assess the effect of L-DOPA on the sympathetic nervous system. The whole vas deferens was used to measure extracellular concentrations of neurotransmitters released after exposure to L-DOPA. In vivo microdialysis was used to assess the effects of exposure to L-DOPA on extracellular NA and metabolites concentrations in the central nervous system.
We showed that acute treatment with L-DOPA and an MAO-A or -A/B inhibitor in the in vitro system (neuronal reuptake and a2-presynaptic receptors blocked) increased NA basal release. The mechanism of this effect may well be similar to that proposed for the ability of DA to increase NA release, i.e. a displacement of NA from storage sites by DA. In the whole animal, L-DOPA/carbidopa was shown to decrease the extracellular levels of NA and increase those of DHPG in frontal cortex microdialysate. This indicates an increased intracellular turnover of NA in cortical axon terminals, which is also most likely to be the result of displacement of NA from intracellular storage sites by increased intracellular DA concentration. The decrease in extracellular NA levels seems to be the result of α2-presynaptic inhibitory receptor activation.