In order to regulate the actions of Dopamine, the Dopaminergic cells, as well as releasing Dopamine, can also suck some of it back into the cell, in order to reduce the Dopamine signalling activity, or terminate the signal of the neurotransmitter.
We have seen how the precursor chemicals of Dopamine, such as Tyrosine and L-Dopa, need a special “Transporter” protein to ferry them across the gut lining out the GI tract into the blood, and across the blood-brain barrier to get out of the blood into the brain. The specific transporter in that case was called “LAT” (Large Amino Acid Transporter).
In an analogous way, active Dopamine outside the cell requires a special transporter protein to ferry it across the cell membrane back to the inside. This is the Dopamine Transporter, or “DAT”.
Dysregulation in the DAT ferrying system is associated with a number of chronic conditions, including ADHD, Bipolar, depression, eating disorders, substance abuse, Parkinson’s, and dystonia. If there is too much DAT activity, it means that there is a deficiency in active Dopamine outside the cell, as it is being pulled back inside the cell constantly. Meanwhile, if there is too little DAT, active Dopamine outside the cell builds, as the re-uptake is slow.
Various drugs and pharmaceutical affect the DAT system, Cocaine, in particular, binds to, and hence ties up, the DAT, so that the transporter is no longer available for ferrying Dopamine.
“As a result, with cocaine on board, dopamine molecules that otherwise would be picked up remain in action. Dopamine builds up and overactivates the receiving cells.”
Amphetamine, on the other, is readily transported by the DAT into the cells, replacing and forcing any inactive Dopamine stored inside out of the cell where it becomes active. The amount of extracellular Dopamine again becomes large, because the drug is then taking up the storage space inside the cell.
Opioids and anti-depressants can also affect the DAT’s ability to bind to Dopamine.
Similar to Dopamine receptors, the amount of DAT available can be up-regulated or down-regulated (change over time).
The concept of DAT points to something really important: when we are talking about low or high Dopamine, or “Dopamine deficiency”, we have to be very careful whether we are referring to active Dopamine outside the cell, or stored Dopamine inside the cell. It can be high in one, while low in the other.
DAT Scans
A “DAT Scan” can be used to peer into the brain and see the level of DAT available. It consists of injecting the person with a radioactive substance that binds to DAT, the location of which can then be picked up with a special camera. The person has to lie still for 40 to 60 minutes.
It is important to note that a DAT Scan does not directly tell one anything about whether Dopamine cells are dead, nor even is a direct measure of how much Dopamine there is. It just measures how much DAT is available for Dopamine outside the cells there is to bind to. Anything else is by inference, proxy, conjecture, or correlation.
Neither do DAT scans say anything about irreversibility, this is again just an inference. It is only a snapshot in time, and DAT levels can change, depending on the environment. DAT levels can both be up-regulated and down-regulated.
Indeed, DAT naturally and adaptively changes in feedback response with Dopamine itself. The important following quote, according to the science article “Molecular Imaging of the Dopamine Transporter“, highlights this point that DAT may be changed as a healthy, adaptive response to the early stages of apparent Dopamine deficiency.
“However, there are several findings that DAT expression is not merely related to the vitality of the nigral neurons, since… involvement could antedate nigral cellular degeneration and DAT density could be modulated as a compensatory mechanism in preclinical/early PD. All of these points, along with several potential external interferences, make DAT imaging a less reliable marker of disease progression.”
“Indeed, reduction of DAT [and hence more Dopamine activity outside the cell, less Dopamine stored in the cell] binding seems to be already present in the [pre-diagnosis] stage of PD, suggesting both an early synaptic dysfunction and the activation of compensatory changes to delay the onset of symptoms. “
Further, the following is according to the science article “Dopamine transporter SPECT imaging in Parkinson’s disease and parkinsonian disorders“:
“in patients with PD, the levels of DAT binding measured with [a DAT Scan] will overestimate the true degree of neurodegeneration in the striatum because of a downregulation of DAT expression in the remaining neurons as an adaptive mechanism to preserve synaptic [active] dopamine levels”.
For example, if one is chronically stressed and hence constantly turning Dopamine supplies into Adrenaline, there will be little stored Dopamine left available for release. It is likely that DAT will then be adaptively down-regulated so that the majority of whatever Dopamine is left over can be active outside the cells. Likewise, if one learns to inhabit the calm state, so that Dopamine is no longer being turned into Adrenaline too quickly, then the DAT levels are eventually likely to go up again, in order that not all the Dopamine is active, and some is stored inside the cell for reserve.
The results of a DAT Scan also have a lot of strong and significant dependencies on equipment, practitioner, software, and technical variable, e.g. on camera, experience of interpreting person, movement of the person being scanned during the procedure, sex and age of person being scanned, exposure time [length of time the person is scanned for], choice of parts of image to be analyzed, software version and settings, database used for comparison. This means there is a significant scope for interpretation differences, so it is as much an art as a science.
Note that while the DAT Scan can distinguish between two broad different classes of neurological condition – those that involve a deterioration of striatal Dopamine in the brain from those that don’t – it should not be used for specific diagnosis, nor as a direct measure of disease progression. Indeed, there is
“… a weak correlation with PD severity and progression”
“… reduced levels of baseline striatal DAT availability on [DAT] scanning, however, should be regarded as supportive rather than diagnostic of dopamine deficient parkinsonism.”