Regional differences in evoked responses in the rat basal ganglia: An in vivo microdialysis study

College

College of Science

Department/Unit

Chemistry

Document Type

Conference Proceeding

Source Title

15th Philippine Chemistry Congress

Publication Date

5-1999

Abstract

The present study demonstrates the application of in vivo microdialysis coupled with high performance liquid chromatography (HPLC) and electrochemical detection (RCD) to the quantification of extracellular levels of dopamine (DA) and serotonin (5-HT) and their major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the rat brain. Specifically, this technique was used to measure levels of the above neurotransmitters/metabolites in two regions of the basal ganglia, the caudate-putamen (CPu) and globus pallidus (GP), after perfusion with normal Ringer’s solution, and after systemic injection with tryptophan side chain oxidase (TSO) I.

Basal concentrations of DA, DOPAC and HVA are highest in CPu while 50HT and 5-HIAA are highest at GP.

Upon exposure to high potassium, there is an increase in measure levels of DA and 5-HT. the high potassium-induced DA release was higher in GP compare to CPu, while 5-HT release was higher in CPu compared to GP. Under high potassium depolarizing conditions, decreases in extracellular levels of DOPAC, HVA and 5-HIAA were observed. Upon repolarization, extracellular levels of DOPAC and HVA increased several-fold before returning to basal levels. By contrast, no corresponding overshoot of 5-HIAA was observed.

On the other hand, perfusion with tyramine caused an increase in measured levels of DA, 5-HT, DOPAC and HVA with no apparent change in measured levels of 5-HIAA. Following exposure to tyramine, higher DA, DOPAC and HVA levels were detected in GP, while higher 5-HT levels were detected in CPu.

Intraperitoneal administration of Tso I selectively depletes 5-HT and 5-HIAA. This depletion is greater in GP than in CPu. By contrast, only minor changes in DA, DOPAC and HVA levels were observed. Evoked responses were still induced by treatments with high potassium and tyramine after TSO I administration, although responses were lower compared to those observed prior to TSO treatment. Larger responses were detected from DA, DOPAC and HVA compared to 5-HT and 5-HIAA.

This study shows clear regional differences in basal and evoked releases of DA, 5-HT, DOPAC, HVA and 5-HIAA in the rat basal ganglia in vivo. These observations thus support the concept of heterogeneity in organization of the basal ganglia. This regional heterogeneity in release profiles may be attributed to structural differences such as origin/quantity of dopaminergic and serotonergic innervations, activities of catabolic enzymes (specifically MAO), efficiencies of neuronal uptake mechanisms, and/or distribution of specific transporters that carry neurotransmitters/metabolites to the extracellular space. Also, the involvement of different regionally distributed neurotransmitter/metabolites acting on presynaptic receptors involved in the regulation of their release, or differences between nerve terminals in striosomes and matrix cannot be excluded.

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Disciplines

Chemistry

Keywords

Neurotransmitters; Dopamine; Serotonin; Metabolites; Basal ganglia

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