EXPLORING EXTRACELLULAR DOPAMINE CONCENTRATION AND ITSudREGULATION ON DOPAMINE RELEASE BY VOLTAMMETRY

摘要

Extracellular dopamine (DA) is critical in regulating DA release as well as interacting with otherudneurotransmission systems. Microdialysis and voltammetry are the major techniques for extracellular DAudmeasurement in vivo. These two techniques provide distinct results due to their different detectionudvolumes. Carbon fiber microelectrode is 10,000 times smaller than that of a microdialysis probe. Withudsuch a small size, carbon fiber microelectrode provides a high spatial resolution and causes unobservableuddamage to the brain which paints a completely different picture of DA release in the brain as compared toudthe knowledge obtained by microdialysis.udIn Chapter I, with the high temporal and spatial resolution provided by carbon fiberudmicroelectrode in conjunction with fast scan cyclic voltammetry (FSCV), we are able to detect DAudterminal populations with different autoinhibition levels in rat striatum. We revealed a coupling betweenudresting DA and local autoinhibition level. The recording sites with high resting DA concentration (micromolar)udexhibit a high autoinhibition on evoked DA release induced by medial forebrain bundle (MFB)udstimulation, and vice versa. These different types of DA release will never be observed by microdialysisuddue to its large dimension. On the contrary, microdialysis result is an average of all the DA release sitesud(high and low) that the microdialysis probe goes through. This averaging method could contribute to theudlow measurement of the DA concentration by microdialysis.udIn Chapter II, we examined the resting DA by a carbon fiber microelectrode at ~200 micron awayudfrom a microdialysis probe. We found TTX-insensitive DA was decreased by microdialysis probeudimplantation. This reduction contributes to the low DA measurement by microdialysis.udIn Chapter III, we monitored evoked DA induced by MFB stimulation in the tissue nearudmicrodialysis probe. We found DA terminals near a microdialysis probe are hyper-sensitive to D2udreceptor antagonist and DA transporter inhibitor. This suggests that the DA terminals in the tissue nearudmicrodialysis probe are under an altered neurochemical state with a loss of DA homeostasis.