Extracellular Dopamine In Striatum Research Articles

Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing cerebral microdialysis.

Unilateral ligation of the left common carotid artery in anesthetized Mongolian gerbils resulted in a steep rise in extracellular dopamine in the ipsilateral striatum in 9 out of 19 animals. Extracellular dopamine was measured by cerebral dialysis in vivo and reached a peak of 0.19 mM at 40 min. At the same time, the level of homovanillic acid fell, whereas the levels of ascorbate and 3,4-dihydroxyphenylacetic acid remained relatively constant. In a separate group of animals studied with a combined dialysis/electrochemistry probe, a rise in the in vivo chronoamperometric signal in three out of six animals correlated with a rise in extracellular dopamine. The number of animals responding in these experiments (roughly 50%) corresponds to the frequency of incompetent Circle of Willis, as well as literature reports of the frequency of signs of stroke in unanesthetized gerbils. These results show a remarkable accumulation of dopamine in extracellular fluid in response to cerebral ischemia. Released dopamine appears to be responsible for the elevated in vivo electrochemical signal previously reported.

Normalization of extracellular dopamine in striatum following recovery from a partial unilateral 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats

It has been hypothesized that striatal dopamine (DA) terminals undergo compensatory changes in response to partial damage of the mesostriatal DA system, which results in higher concentrations of DA in the extracellular space than would be predicted by DA concentrations in post-mortem tissue. But, this hypothesis has never been tested directly in vivo, and therefore, the present study was designed to do so. Microdialysis was used in freely moving rats to estimate the concentrations of DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in striatal extracellular fluid; simultaneously from the hemisphere with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra and from the intact hemisphere. It was found that following recovery from a 6-OHDA lesion, and during the resting state, the extracellular concentrations of DA were normal on the lesion side, even after that side was depleted of up to 99.0% of the DA measured in post-mortem tissue. Furthermore, the extracellular concentrations of DA were elevated in the intact hemisphere of animals with a >95% DA depletion. In rats with a <95% DA depletion amphetamine (1.5 mg/kg) caused a large increase in the extracellular concentration of DA in both the lesion and intact hemispheres (intact > lesion), but in rats with a > 95% tissue DA depletion amphetamine only enhanced extracellular DA on the intact side; on the lesion side amphetamine produced a progressive decrease in extracellular DA to nondetectable levels. Animals rotated towards the lesion side. Unlike DA, the extracellular concentrations of DOPAC and HVA were greatly reduced on the lesion side, and the extent of the depletion was highly correlated with lesion size. It is concluded that following partial unilateral damage to mesostriatal DA projections there are massive changes in the remaining DA terminals that are sufficient to normalize the extracellular (and presumably synaptic) concentrations of DA. The normalization of extracellular DA concentrations seen after extensive (but incomplete) damage to the mesostriatal system must play a major role in the sparing and recovery of behavioral function that is so characteristic of this system. After extensive damage the capacity of the remaining DA neurons to respond to increased demand is limited, however, and this may explain why behavioral deficits can be reinstated by stimuli that challenge the system.