Brain & Behavior Research Foundation NARSAD Grantee Kathryn A. Cunningham, Ph.D., with her team at University of Texas Medical Branch (UTMB), Galveston and collaborators at the University of Houston (UH), has found a new way to influence the vital serotonin signaling system—possibly leading to more effective medications with fewer side effects. The findings were published online in the Journal of Neuroscience on Jan. 23, 2013.

It is known that malfunctions in serotonin signaling play a role in many illnesses, including depression. Much research has focused on complex proteins called serotonin receptors at their so-called "active site" that is specially suited to bond with a serotonin molecule. When the bond is formed, the receptor changes shape, transmitting a signal to the cell's interior. Traditional medications target these active sites.

In this new approach, additional proteins are targeted that bind to the receptor at locations quite distant (in molecular terms) from the active site. "This is a whole new way of thinking about this system, targeting these interactions,” says senior author Dr. Kathryn Cunningham, professor, UTMB. “Basically, we've created a new series of molecules and validated that we can use them to change the way the [serotonin] receptor functions… I think in a broader sense this is really going to help us understand the neurobiology of these disorders [addictions, alcoholism, depression and obesity and eating disorders]."The researchers used both human cells and animal models in the research to enable closer “translation” of the research into potential new medications.

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Read the Journal of Neuroscience article