New Perspectives on Neurotransmitter Malfunction

Doctor Randy Blakely speculates that the traditional view that drugs though to increase serotonin and dopamine levels in the brain may work by preventing a backward-running state.

What is interesting about the convergence of information on Adderal or amphetamine and Ritalin or methylphenidate in the treatment of ADHD for our two boys and for this mutation is that, in vitro, in the laboratory, these two drugs oppose each other. They do not act the same way. So, over the last several decades, explanations for the common therapeutic benefit of these drugs have generally gone in the direction of that it can’t be explained at the molecular level. We need circuits, we need to think about how the brain develops, in order to understand why these two drugs that oppose each other in vitro work in the same way in vivo. So what we have shown now is that if the dopamine transporter gets into this backward running state, then these two drugs in vitro work the same and in vivo work the same. To us, this is a strong signal that in fact this backward running state of the dopamine transporter could underlie the disorder in many individuals who are effectively treated with these medications. So that hypothesis then leads you to ask one more question, and that is, if we give kids a transporter blocker like methylphenidate, therapeutically, to stop this backward-running of the transporter, is that backward-running state common to other transporters found in other diseases? Because, we give other transporter blockers clinically; we give serotonin transporter blockers, for example, to treat depression. The way we treat our medical students and out clinicians is that the reason those drugs are effective is because they elevate serotonin levels in the brain. And they do that, but our hypothesis now is that they may be blocking an inappropriately backward movement of serotonin out of the neuron, into the extracellular space, and it’s blocking the leak that’s really more important than is boosting serotonin levels. So, maybe there is something more general here. And in the next year or two, we hope to pursue that idea much more actively.