Dopamine Transporter Networks

Doctor Randy Blakely discusses the potential role of the dopamine transporter (DAT) as one element of a complex protein network in ADHD and bipolar disorder.

Imagine you have a dopamine transporter that has to be turned on and off at different times, due to changes in dopamine signaling. Sometimes there’s a lot of dopamine there and you need to take it away; sometimes there’s not very much dopamine there, and you really should reduce your dopamine transporter activity, or you might even get into an area where you don’t have sufficient dopamine. So, the neuron has to figure all of that out; it has to regulate its dopamine transporters tightly. That’s a normal homeostatic mechanism, and it has pushes and pulls on it; there are proteins that we know enhance the amount of dopamine transporter that are produced and are delivered to the synapse, and then there are proteins that take it away. One can speculate at this point that there might be changes in the networks of proteins that control the dopamine transporter that are now out of balance and deliver it inappropriately, leading to, sometimes excess dopamine and sometimes insufficient dopamine. Time will tell if that is a reasonable hypothesis. We’re now on the trail of other dopamine transporter gene variants in bipolar disorder directly; we’ve made a serious attempt to go directly into this disorder now, and see if we can, in fact, find such changes, but that’s the model that we’re working with.