Grant: Project Grant

Dopamine transmission in the brain is a tightly regulated process, and alterations in dopamine signaling result in several disease with enormous human and economic burden, including schizophrenia, ADHD, Bipolar disorder, Parkinson's disease and dyskinesias. One of the key regulators of dopamine transmission is the plasma membrane dopamine transporter, DAT, which transports released dopamine back into the neuron. In addition to the above prevalent diseases, there is also a rare, fatal disease caused by mutations in the dopamine transporter, called dopamine transporter deficiency syndrome. We hypothesize that several disease states could be corrected by increasing the protein levels of the dopamine transporter. Drugs that increase dopamine transporter activity could potentially treat conditions such as such as dopamine transporter deficiency syndrome. We have worked to identify drugs that would increase the levels and activity of the dopamine transporter, and have discovered that the prescribed drug bupropion increases dopamine transporter levels and activity. Recently, we generated a transgenic mouse model of dopamine transporter deficiency syndrome. Our proposed research is designed to uncover the pathophysiology of this by studying these new transgenic animals. Also, we will measure whether bupropion will be able to have therapeutic effect in this new mouse model. Positive results from our studies could be quickly translated into the clinic, since bupropion is already an approved drug and used in humans.