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Exploring extracellular dopamine concentration and its regulation on dopamine release by voltammetry

Extracellular dopamine (DA) is critical in regulating DA release as well as interacting with other 
neurotransmission systems. Microdialysis and voltammetry are the major techniques for extracellular DA 
measurement in vivo. These two techniques provide distinct results due to their different detection 
volumes. Carbon fiber microelectrode is 10,000 times smaller than that of a microdialysis probe. With 
such a small size, carbon fiber microelectrode provides a high spatial resolution and causes unobservable 
damage to the brain which paints a completely different picture of DA release in the brain as compared to 
the knowledge obtained by microdialysis. 
In Chapter I, with the high temporal and spatial resolution provided by carbon fiber 
microelectrode in conjunction with fast scan cyclic voltammetry (FSCV), we are able to detect DA 
terminal populations with different autoinhibition levels in rat striatum. We revealed a coupling between 
resting DA and local autoinhibition level. The recording sites with high resting DA concentration (micromolar) 
exhibit a high autoinhibition on evoked DA release induced by medial forebrain bundle (MFB) 
stimulation, and vice versa. These different types of DA release will never be observed by microdialysis 
due to its large dimension. On the contrary, microdialysis result is an average of all the DA release sites 
(high and low) that the microdialysis probe goes through. This averaging method could contribute to the 
low measurement of the DA concentration by microdialysis. 
In Chapter II, we examined the resting DA by a carbon fiber microelectrode at ~200 micron away 
from a microdialysis probe. We found TTX-insensitive DA was decreased by microdialysis probe 
implantation. This reduction contributes to the low DA measurement by microdialysis. 
In Chapter III, we monitored evoked DA induced by MFB stimulation in the tissue near 
microdialysis probe. We found DA terminals near a microdialysis probe are hyper-sensitive to D2 
receptor antagonist and DA transporter inhibitor. This suggests that the DA terminals in the tissue near 
microdialysis probe are under an altered neurochemical state with a loss of DA homeostasis.