BIOTRANSFORMATION OF LOCALLY APPLIED PRECURSORS OF DOPAMINE, SEROTONIN AND NORADRENALINE IN STRIATUM AND HIPPOCAMPUS - A MICRODIALYSIS STUDY

In vivo microdialysis in freely moving rats was used to study the biot ransformation, consisting primarily of decarboxylation by aromatic ami no acid decarboxylase (AAAD), of the precursors L-3,4-dihydroxyphenyla lanine (L-DOPA), L-5-hydroxytryptophan (L-5HTP), and L-threo-3,4-dihyd roxyphenylserine (L-threo-DOPS) on extracellular levels of dopamine (D A), serotonin (5HT) and noradrenaline (NA), respectively. The precurso rs were administered locally through the microdialysis probe into the striatum and into the hippocampus. The different transmitter systems w ere compared with respect to the ability of the precursors to elevate extracellular levels of their associated transmitter. The basal extrac ellular concentrations of NA and DA were found to be tetrodotoxin (TTX , a blocker of fast sodium channels) sensitive in striatum and hippoca mpus, indicating the neuronal origin of the measured transmitters. The extracellular concentrations of 5HT (in hippocampus) were only 60% TT X-sensitive. L-DOPA and L-SHTP showed to be effective precursors of DA and 5HT, respectively, although their formation profile was quite dif ferent. The L-DOPA-induced increase in extracellular DA was large and short-lasting, while the L-5HTP-induced increase in 5HT was slower and less pronounced. The relative increase in extracellular;DA or 5HT was more pronounced in the brain region where their baseline values were lower, but the absolute amount of transmitter formed from their precur sor was similar in both brain regions. L-threo-DOPS was a poor precurs or for NA and also failed to influence extracellular DA in striatum, q uestioning its use in the treatment of freezing gait in late stages of Parkinson's disease.